Antibodies against tight junction protein 6 comprising bispecific versions

Abstract

The present disclosure relates to antibodies specific for tight junction protein 6 and CD3 and methods of making and using the same. The present disclosure describes the isolation and characterization of antibodies, antibody fragments, and antibody variants that are specific for tight junction proteins 6 and CD3.

Description

[0001] Related Applications

[0002] This application claims the benefit of U.S. Provisional Application Serial No. 63 / 385,535, filed November 30, 2022; U.S. Provisional Application Serial No. 63 / 496,174, filed April 14, 2023; U.S. Provisional Application Serial No. 63 / 506,533, filed June 6, 2023; U.S. Provisional Application Serial No. 63 / 517,668, filed August 4, 2023; and U.S. Provisional Application Serial No. 63 / 591,924, filed October 20, 2023, each of which is hereby incorporated by reference in its entirety. Technical Field

[0003] The present disclosure relates to compositions and related methods that bind to claudin-6.

[0004] Sequence Listing

[0005] This application contains a sequence listing that has been electronically submitted in XML format and is hereby incorporated by reference in its entirety. The XML copy was created on November 28, 2023, has the name "INM-001PC_122086-5001 Sequence Listing", and is 142,000 bytes in size. Background Art

[0006] Cell adhesion proteins are essential for maintaining tissue integrity and regulating various cellular events in multiple physiological and pathological processes. Among cell adhesion proteins, some members of the claudin (CLDN) family are frequently aberrantly expressed in various cancers. Due to the lack of antibody specificity for specific CLDN proteins and the widespread expression of closely related CLDN family members in normal cells, the clinical application of CLDN therapeutics has been difficult. Thus, there remains a great need for improved compositions and methods that can modulate the activity of CLDN family members to treat various cancers and diseases. Summary of the Invention

[0007] Accordingly, in various aspects, the present disclosure relates to a composition that specifically binds to claudin 6 and CD3. The present disclosure describes the isolation and characterization of antibodies, antibody fragments, and antibody variants that are specific for claudin 6 and CD3. In some embodiments, the antibody that is specific for claudin 6 and CD3 is a tandem single-chain variable fragment (scFv). In some embodiments, the antibody that is specific for claudin 6 and CD3 is an scFv-Fab Fc antibody that is specific for claudin 6 and CD3. In some embodiments, the antibody that is specific for claudin 6 and CD3 is an IgG-(scFv)2 antibody that is specific for claudin 6 and CD3. In some embodiments, the antibody that is specific for claudin 6 and CD3 is an scFv-Fab Fc that is specific for claudin 6 and CD3. In some embodiments, the antibody that is specific for claudin 6 and CD3 binds to both claudin 6 and CD3 simultaneously.

[0008] In some embodiments, the present disclosure provides a composition comprising an scFv-Fab Fc antibody that is specific for claudin 6 and CD3, the antibody comprising:

[0009] (a) a first heavy chain selected from:

[0010] (i) SEQ ID NO:79,

[0011] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0012] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[0013] (ii) SEQ ID NO:88,

[0014] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0015] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0016] or

[0017] (iii) SEQ ID NO:114,

[0018] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0019] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof,

[0020] (b) A second heavy chain, the second heavy chain selected from:

[0021] (i.) SEQ ID NO:80,

[0022] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0023] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, or

[0024] (ii.) SEQ ID NO:89,

[0025] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0026] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, or

[0027] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, or

[0028] (iii.) SEQ ID NO: 90,

[0029] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0030] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof, or

[0031] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 48 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof, or

[0032] (iv.) SEQ ID NO: 91,

[0033] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0034] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of ID NO: 21 or a variant thereof, or

[0035] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 49 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof, or

[0036] (v.) SEQ ID NO: 92,

[0037] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0038] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof, or

[0039] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof, or

[0040] (vi.) SEQ ID NO: 111,

[0041] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0042] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof, or

[0043] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof,

[0044] and

[0045] (c) A first light chain selected from:

[0046] (i) SEQ ID NO: 67,

[0047] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0048] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0049] (ii) SEQ ID NO: 66,

[0050] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0051] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of ID NO: 3 or a variant thereof,

[0052] or

[0053] (iii) SEQ ID NO: 65,

[0054] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0055] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, or

[0056] wherein:

[0057] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N-terminus or C-terminus, and

[0058] Any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0059] In some embodiments, the Fc is from IgG.

[0060] In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0061] In some embodiments, the antibody is formed by a knob-in-hole interaction in the Fc region. In some embodiments, the human IgG Fc contains one or more mutations to facilitate the knob-in-hole interaction. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are selected from:

[0062] (a) T366Y and Y407T in human IgG1 or T366Y / F405A and T394W / Y407T, or

[0063] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0064] T366W / K392C and T366S / L368A / D399C / Y407V;

[0065] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0066] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0067] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0068] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0069] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0070] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0071] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1.

[0072] In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0073] In some embodiments, a composition is disclosed herein that comprises an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising:

[0074] (a) a first heavy chain selected from:

[0075] (i) SEQ ID NO:79,

[0076] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0077] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0078] (ii) SEQ ID NO:88,

[0079] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0080] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[0081] or

[0082] (iii) SEQ ID NO: 114,

[0083] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0084] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof,

[0085] (b) A second heavy chain, said second heavy chain selected from:

[0086] SEQ ID NO: 81,

[0087] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0088] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0089] and

[0090] (c) A light chain, said light chain selected from:

[0091] (i) SEQ ID NO: 67,

[0092] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0093] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0094] (ii) SEQ ID NO:66

[0095] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0096] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0097] or

[0098] (iii) SEQ ID NO:65,

[0099] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0100] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[0101] wherein:

[0102] any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0103] any of the above sequences optionally has a linker comprising one or more glycines and serines, and said linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0104] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0105] In some embodiments, antibodies are formed by knob-in-hole interactions in the Fc region. In some embodiments, human IgG Fc contains one or more mutations to facilitate knob-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are:

[0106] (a) T366Y and Y407T in human IgG1, or T366Y / F405A and T394W / Y407T, or

[0107] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0108] T366W / K392C and T366S / L368A / D399C / Y407V;

[0109] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0110] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0111] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0112] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0113] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0114] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0115] In some embodiments, human IgG Fc contains one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, human IgG Fc contains one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0116] In some embodiments, a composition is disclosed herein that comprises an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising:

[0117] (a) A first heavy chain selected from:

[0118] (i) SEQ ID NO:79,

[0119] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0120] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0121] (ii) SEQ ID NO:88,

[0122] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0123] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0124] or

[0125] (iii) SEQ ID NO:114,

[0126] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0127] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof,

[0128] (b) A second heavy chain selected from:

[0129] (i.) SEQ ID NO:117,

[0130] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0131] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0132] or

[0133] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0134] (ii.) SEQ ID NO:119,

[0135] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0136] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0137] or

[0138] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0139] (iii.) SEQ ID NO:118,

[0140] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0141] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0142] or

[0143] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[0144] (iv.) SEQ ID NO: 120,

[0145] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0146] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0147] or

[0148] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[0149] and

[0150] (c) A light chain selected from:

[0151] (i) SEQ ID NO: 67,

[0152] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0153] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0154] (ii) SEQ ID NO:66

[0155] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0156] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0157] or

[0158] (iii) SEQ ID NO:65,

[0159] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0160] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[0161] wherein:

[0162] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0163] Any of the above sequences optionally has a linker comprising one or more glycines and serines, and said linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0164] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0165] In some embodiments, antibodies are formed by knob-in-hole interactions in the Fc region. In some embodiments, human IgG Fc contains one or more mutations to facilitate knob-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are:

[0166] (a) T366Y and Y407T in human IgG1, or T366Y / F405A and T394W / Y407T, or

[0167] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0168] T366W / K392C and T366S / L368A / D399C / Y407V;

[0169] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0170] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0171] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0172] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0173] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0174] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0175] In some embodiments, human IgG Fc contains one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, human IgG Fc contains one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0176] In some embodiments, a composition is disclosed herein that comprises an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising:

[0177] (a) A first heavy chain selected from:

[0178] (i) SEQ ID NO:79,

[0179] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0180] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[0181] (ii) SEQ ID NO:88,

[0182] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0183] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0184] or

[0185] (iii) SEQ ID NO:114,

[0186] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0187] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof,

[0188] (b) A second heavy chain selected from:

[0189] (i) SEQ ID NO:121,

[0190] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0191] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof,

[0192] (ii) SEQ ID NO:123,

[0193] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0194] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof,

[0195] (iii) SEQ ID NO:125,

[0196] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0197] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof,

[0198] (iv) SEQ ID NO:127,

[0199] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0200] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, or

[0201] (v) SEQ ID NO:129,

[0202] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0203] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof,

[0204] and

[0205] (c) A first light chain, the first light chain being selected from:

[0206] (i) SEQ ID NO:67,

[0207] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0208] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0209] (ii) SEQ ID NO:66,

[0210] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0211] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0212] or

[0213] (iii) SEQ ID NO: 65,

[0214] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0215] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0216] and

[0217] (d) A second light chain selected from:

[0218] (i) SEQ ID NO: 122,

[0219] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0220] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, or

[0221] (ii) SEQ ID NO: 124,

[0222] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0223] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof, or

[0224] (iii) SEQ ID NO: 126,

[0225] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0226] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of ID NO: 22 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof, or

[0227] (iv) SEQ ID NO: 128,

[0228] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0229] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof, or

[0230] (v) SEQ ID NO: 130,

[0231] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0232] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof, or

[0233] wherein:

[0234] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0235] Any of the above sequences optionally has a linker containing one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0236] In some embodiments, a bispecific antibody is disclosed herein, wherein the bispecific antibody comprises three polypeptides (e.g., a first polypeptide, a second polypeptide, and a third polypeptide) that form a first antigen-binding domain that binds CLDN6 and a second antigen-binding domain that binds CD3. In some embodiments, the first polypeptide comprises a first light chain that comprises a first variable light chain region (first V L L), wherein the first variable light chain region comprises a CDR1 sequence having the amino acid sequence of SEQ ID NO:1, a CDR2 sequence having the amino acid sequence of SEQ ID NO:2, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:3. In some embodiments, the second polypeptide comprises a first heavy chain that comprises a first variable heavy chain region (first V H H), wherein the first variable heavy chain region comprises a CDR1 sequence having the amino acid sequence of SEQ ID NO:4, a CDR2 sequence having the amino acid sequence of SEQ ID NO:5, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:6. In some embodiments, the third polypeptide comprises a second heavy chain and a second light chain, wherein the second heavy chain comprises a second variable heavy chain region (second V H H), and the second variable heavy chain region comprises a CDR1 sequence having the amino acid sequence of SEQ ID NO:25, a CDR2 sequence having the amino acid sequence of SEQ IDNO:26, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:27; wherein the second light chain comprises a second variable light chain region (second V L), the second variable light chain region comprises a CDR1 sequence containing the amino acid sequence of SEQ ID NO:28, a CDR2 sequence containing the amino acid sequence of SEQ ID NO:29, and a CDR3 sequence containing the amino acid sequence of SEQ ID NO:30. In some embodiments, the second heavy chain and the second light chain are linked by a peptide linker. In some embodiments, the peptide linker is as described herein. In some embodiments, the peptide linker comprises the amino acid sequence of (GKPGSGKPGSGKPGSGKPGSG) SEQ ID NO:53. In some embodiments, the peptide linker comprising one or more glycines and serines is replaced by another peptide linker or a functional equivalent variant thereof. In some embodiments, the first V L and the first V H interact to form an antigen-binding domain that binds to CLDN6. In some embodiments, the second V L and the second V H interact to form an antigen-binding domain that binds to CD3. In some embodiments, the second V L and the second V H are in the scFv format. In some embodiments, the first V L and the first V H are in the Fab format or a fragment thereof.

[0237] In some embodiments, the first variable light chain region of the first polypeptide comprises the amino acid sequence of SEQ ID NO:68, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0238] In some embodiments, the first variable heavy chain region of the second polypeptide comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0239] In some embodiments, the second variable heavy chain region of the third polypeptide comprises the amino acid sequence of SEQ ID NO:70, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0240] In some embodiments, the second variable light chain region of the third polypeptide comprises the amino acid sequence of SEQ ID NO:71, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0241] In some embodiments, the first polypeptide that impairs the light chain comprises a first variable light chain region and a light chain constant domain that can be referred to as the first light chain constant domain. In some embodiments, the first light chain constant domain comprises the amino acid sequence of SEQ ID NO:72, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0242] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO:67, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0243] In some embodiments, the second polypeptide that impairs the first heavy chain comprises a first variable heavy chain region and a heavy chain constant domain that can be referred to as the first heavy chain constant domain. In some embodiments, the first heavy chain constant domain comprises the amino acid sequence of SEQ ID NO:73, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0244] In some embodiments, the second polypeptide comprises the amino acid sequence of SEQ ID NO:79, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0245] In some embodiments, the third polypeptide comprises a constant domain. In some embodiments, the constant domain is linked to the C-terminus of the second variable light chain region. In some embodiments, there is no peptide linker between the C-terminus of the second variable light chain region and the constant domain. In some embodiments, the constant domain present in the third polypeptide comprises the amino acid sequence of SEQ ID NO:74, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0246] In some embodiments, the third polypeptide comprises the amino acid sequence of SEQ ID NO:89, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0247] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO:67; the second polypeptide comprises the amino acid sequence of SEQ ID NO:79; and the third polypeptide comprises the amino acid sequence of SEQ ID NO:89.

[0248] As used herein, the term constant domain refers to the Fc domain. The constant domains illustrated above are optional embodiments, and other constant domains may replace the constant domains described herein.

[0249] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0250] In some embodiments, the antibody is formed by knob-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc contains one or more mutations to facilitate knob-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are:

[0251] (a) T366Y and Y407T in human IgG1, or T366Y / F405A and T394W / Y407T, or

[0252] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0253] T366W / K392C and T366S / L368A / D399C / Y407V;

[0254] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0255] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0256] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0257] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0258] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0259] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0260] In some embodiments, the human IgG Fc contains one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc contains one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0261] In some embodiments, the composition binds both claudin 6 and CD3 simultaneously.

[0262] In some embodiments, the composition binds claudin 6 with an affinity less than 10 nM and an affinity at least 100-fold that for claudin 9, claudin 3, and / or claudin 4.

[0263] In some embodiments, there is provided a pharmaceutical composition comprising the isolated antibody or nucleic acid molecule encoding the antibody as described in any one of the foregoing embodiments. In some embodiments, the composition is an injectable pharmaceutical composition. In some embodiments, the composition is sterile. In some embodiments, the composition is pyrogen-free.

[0264] In some embodiments, there is provided a nucleic acid molecule encoding the antibody or amino acid sequence as described in any one of the foregoing embodiments.

[0265] In some embodiments, there is provided a vector comprising the nucleic acid molecule as described in any one of the foregoing embodiments.

[0266] In some embodiments, there is provided a cell comprising the nucleic acid molecule as described in any one of the foregoing embodiments or the vector as described in any one of the foregoing embodiments.

[0267] In some embodiments, there is provided a method for modulating and / or targeting claudin 6 and CD3 in biological cells, the method comprising contacting the cells with the composition as described in any one of the foregoing embodiments.

[0268] In some embodiments, there is provided a method for modulating the activity of claudin 6 in biological cells, the method comprising contacting cells expressing claudin 6 with the composition as described in any one of the foregoing embodiments.

[0269] In some embodiments, there is provided a method for inhibiting the function of claudin 6 in biological cells, the method comprising contacting cells expressing claudin 6 with the composition as described in any one of the foregoing embodiments.

[0270] In some embodiments, a method for treating or preventing cancer is disclosed herein, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of the foregoing embodiments.

[0271] In some embodiments, the use of the composition of any one of the foregoing embodiments in the preparation of a medicament for treating or preventing cancer is disclosed herein.

[0272] In some embodiments, the method or use of any one of the foregoing embodiments is disclosed herein, wherein the cancer is selected from one or more of the following: basal cell carcinoma; biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; peritoneal cancer; cervical cancer; choriocarcinoma; colon and rectal cancer; connective tissue cancer; digestive system cancer; endometrial cancer; esophageal cancer; eye cancer; head and neck cancer; gastric cancer (including gastrointestinal cancer); glioblastoma; liver cancer; hepatocellular carcinoma; intraepithelial neoplasia; kidney cancer or renal carcinoma; laryngeal cancer; leukemia; liver cancer; lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma); melanoma; myeloma; neuroblastoma; oral cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; respiratory system cancer; salivary gland cancer; sarcoma; skin cancer; squamous cell carcinoma; gastric cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; urinary system cancer; vulvar cancer; lymphoma, including Hodgkin's and non-Hodgkin's lymphoma, and B-cell lymphoma (including low-grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocyte (SL) NHL; intermediate / follicular NHL; intermediate diffuse NHL; high-grade immunoblastic NHL; high-grade lymphoblastic NHL; high-grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenström's macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphocytic leukemia (ALL); hairy cell leukemia; chronic myelogenous leukemia; and other carcinomas and sarcomas; and post-transplant lymphoproliferative disorder (PTLD), and abnormal vascular proliferation associated with nevus flammeus, edema (e.g., edema associated with brain tumors), and Meigs' syndrome.

[0273] In some embodiments, an isolated antibody is disclosed herein, the isolated antibody comprising one or more sequences of the sequences disclosed herein.

[0274] Details of one or more embodiments of the present disclosure are set forth in the following description. Other features or advantages of the present disclosure will become apparent from the following drawings, detailed description of several embodiments, and from the appended claims. Details of the present disclosure are set forth in the following accompanying description. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, illustrative methods and materials are now described. Other features, objects, and advantages of the present disclosure will become apparent from the specification and claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. BRIEF DESCRIPTION OF THE DRAWINGS

[0275] Figure 1 Images showing exemplary bispecific formats, including tandem scFv (left), scFv-Fab IgG (middle), and IgG-(scFv)2 (right).

[0276] Figure 2 Is a schematic diagram showing the CLDN6 structure and an image illustrating some challenges in developing an antibody specific to CLDN6.

[0277] Figure 3 Is a graph of RNA sequencing data showing how Claudin 6 is overexpressed in multiple cancers including ovarian cancer, lung cancer, endometrial cancer, and gastric cancer.

[0278] Figure 4 Is an image showing non-limiting monospecific challenges in developing an antibody specific to Claudin 6, as the antibody needs to distinguish between single amino acid side chains at residue 156 on CLDN6 and CLDN9.

[0279] Figure 5 Is a chart showing an overview of data related to four selected antibodies.

[0280] Figure 6 Shows graphs and images of quality control data from the IMC-16-3scFv-Fab IgG antibody (SEQ ID NO:79, 67, and 89).

[0281] Figure 7 Shows graphs and images of quality control data from the IMC-16-15scFv-Fab IgG antibody (SEQ ID NO:114, 65, and 89).

[0282] Figure 8Shown are graphs and images of quality control data from the IMC-21-1 IgG-(scFv)2 antibody (SEQ ID NOs: 86 and 67).

[0283] Figure 9 Shown are graphs and images of quality control data from the IMC-2-7 tandem scFv antibody (SEQ ID NO: 95).

[0284] Figure 10 Two graphs showing target binding data from flow cytometry experiments are shown. Figure 10 The left panel shows target binding data of IMC-16-3scFv-Fab IgG antibody (circles), IMC-16-15scFv-Fab IgG antibody (squares), IMC-21-1IgG-(scFv)2 antibody (triangles), and IMC-2-7 tandem scFv antibody (inverted triangles) to human CLDN6. Figure 10 The right panel shows target binding data of IMC-16-3scFv-Fab IgG antibody (circle), IMC-16-15scFv-Fab IgG antibody (square), IMC-21-1IgG-(scFv)2 antibody (triangle), and IMC-2-7 tandem scFv antibody (inverted triangle) to human CD3. Figure 10 The bottom table shows the binding EC50 data of the molecules against CLDN6 and CD3.

[0285] Figure 11A , Figure 11B , Figure 11C and Figure 11D is a graph showing parental and benchmark antibody binding data from flow cytometry experiments. Figure 11A is a graph showing the binding of IM271-1 HEP antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). Figure 11B is a graph showing the binding of IM271-1HHP antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). Figure 11C is a graph showing the binding of IM271-1HFJ antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds). Figure 11D is a graph showing the binding of antibodies to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and a negative control (diamonds).

[0286] Figure 12A , Figure 12B , Figure 12C and Figure 12D are graphs showing target binding data from flow cytometry experiments. Figure 12A is a graph showing the binding of the IMC-2-7 tandem scFv antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and negative control (diamonds). Figure 12B is a graph showing the binding of the IMC-16-3 scFv-Fab IgG antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and negative control (diamonds). Figure 12C is a graph showing the binding of the IMC-16-15 scFv-Fab IgG antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and negative control (diamonds). Figure 12D is a graph showing the binding of the IMC-21-1 IgG-(scFv)2 antibody to human CLDN6 (circles), human CLDN4 (squares), human CLDN3 (triangles), human CLDN9 (inverted triangles), and negative control (diamonds).

[0287] Figure 13 Shows two graphs of cytotoxicity data from a T cell-dependent cytotoxicity experiment. Figure 13 The left graph of shows the cytotoxicity data of the IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-2-7 tandem scFv antibody, and IMC-16-C2 antibody (negative control) in ovarian cancer OV-90 cells. Figure 13 The right graph of shows the target binding data of the IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-2-7 tandem scFv antibody, and IMC-16-C2 antibody in HEK cells.

[0288] Figure 14A , Figure 14B , Figure 14C , Figure 14D and Figure 14E is a graph showing cytokine production by human PBMCs co-cultured with CLDN6-positive OV-90 cells in the presence or absence of the IMC-16-3 scFv-Fab IgG antibody. Figure 14AShows the results of IL-2 production, Figure 14B shows the results of IL-6 production, Figure 14C shows the results of IL-10 production, Figure 14D shows the results of IFN-γ production, and Figure 14E shows the results of TNF-α production.

[0289] Figure 15A 、 Figure 15B 、 Figure 15C 、 Figure 15D and Figure 15E are graphs showing cytokine production by human PBMCs co-cultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-16-15scFv-FabIgG. Figure 15A shows the results of IL-2 production, Figure 15B shows the results of IL-6 production, Figure 15C shows the results of IL-10 production, Figure 15D shows the results of IFN-γ production, and Figure 15E shows the results of TNF-α production.

[0290] Figure 16A 、 Figure 16B 、 Figure 16C 、 Figure 16D and Figure 16E are graphs showing cytokine production by human PBMCs co-cultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-21-1IgG-(scFv)2 antibody. Figure 16A shows the results of IL-2 production, Figure 16B shows the results of IL-6 production, Figure 16C shows the results of IL-10 production, Figure 16D shows the results of IFN-γ production, and Figure 16E shows the results of TNF-α production.

[0291] Figure 17A 、 Figure 17B 、 Figure 17C 、 Figure 17D and Figure 17E are graphs showing cytokine production by human PBMCs co-cultured with CLDN6-positive OV-90 cells in the presence or absence of IMC-2-7 tandem scFv antibody. Figure 17A shows the results of IL-2 production, Figure 17B shows the results of IL-6 production, Figure 17C shows the results of IL-10 production, Figure 17D shows the results of IFN-γ production, and Figure 17EThe results of TNF-α production are shown.

[0292] Figure 18 A graph showing the cytotoxicity data from the T cell-dependent cytotoxicity experiment. Figure 18 Shows the cytotoxicity data of IMC-2-7 tandem scFv antibody, IMC-16-3 scFv-Fab IgG antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody and negative control (CKV063 LALA) in K562 cells. Figure 18 The table on the right shows the EC50 values of cytotoxicity.

[0293] Figure 19A 、 Figure 19B 、 Figure 19C 、 Figure 19D 、 Figure 19E 、 Figure 19F 、 Figure 19G and Figure 19H Are graphs showing the cytotoxicity and IFN-γ release efficacy data at 24 hours and 48 hours from the cytotoxicity experiment. Figure 19A Shows the cytotoxicity and IFN-γ release data of IMC-16-3 scFv-Fab IgG antibody at 24 hours. Figure 19B Shows the cytotoxicity and IFN-γ release data of IMC-16-15 scFv-Fab IgG antibody at 24 hours. Figure 19C Shows the cytotoxicity and IFN-γ release data of IMC-21-1 IgG-(scFv)2 antibody at 24 hours. Figure 19D Shows the cytotoxicity and IFN-γ release data of IMC-2-7 tandem scFv antibody at 24 hours. Figure 19E Shows the cytotoxicity and IFN-γ release data of IMC-16-3 scFv-Fab IgG antibody at 48 hours. Figure 19F Shows the cytotoxicity and IFN-γ release data of IMC-16-15 scFv-Fab IgG antibody at 48 hours. Figure 19G Shows the cytotoxicity and IFN-γ release data of IMC-21-1 IgG-(scFv)2 antibody at 48 hours. Figure 19H Shows the cytotoxicity and IFN-γ release data of IMC-2-7 tandem scFv antibody at 48 hours. In each experiment, the CKV063 LALA antibody is the negative control.

[0294] Figure 20A 、 Figure 20B 、 Figure 20C 、 Figure 20D 、Figure 20E , Figure 20F , Figure 20G , Figure 20H , Figure 20I and Figure 20J are graphs showing cytotoxicity and IFN-γ release efficacy data at 24 hours and 48 hours from the cytotoxicity experiment. Figure 20A Shows the cytotoxicity and IFN-γ release data of the IMC-16-7 antibody (SEQ ID NO: 79, 67, and 91) at 24 hours. Figure 20B Shows the cytotoxicity and IFN-γ release data of the IMC-2-7 tandem scFv antibody at 24 hours. Figure 20C Shows the cytotoxicity and IFN-γ release data of the IMC-16-3 scFv-Fab IgG antibody at 24 hours. Figure 20D Shows the cytotoxicity and IFN-γ release data of the IMC-16-15 scFv-Fab IgG antibody at 24 hours. Figure 20E Shows the cytotoxicity and IFN-γ release data of the IMC-21-1 IgG-(scFv)2 antibody at 24 hours. Figure 20F Shows the cytotoxicity and IFN-γ release data of the IMC-16-7 antibody at 48 hours. Figure 20G Shows the cytotoxicity and IFN-γ release data of the IMC-2-7 tandem scFv antibody at 48 hours. Figure 20H Shows the cytotoxicity and IFN-γ release data of the IMC-16-3 scFv-Fab IgG antibody at 48 hours. Figure 20I Shows the cytotoxicity and IFN-γ release data of the IMC-16-15 scFv-Fab IgG antibody at 48 hours. Figure 20J Shows the cytotoxicity and IFN-γ release data of the IMC-21-1 IgG-(scFv)2 antibody at 48 hours. In each experiment, the CKV063 LALA antibody is the negative control.

[0295] Figure 21A , Figure 21B , Figure 21C , Figure 21D , Figure 21E , Figure 21F , Figure 21G , Figure 21H , Figure 21I and Figure 21J are graphs showing cytotoxicity and IL-2 release efficacy data at 24 hours and 48 hours from the cytotoxicity experiment. Figure 21ACytotoxicity and IL-2 release data for IMC-16-7 antibodies (SEQ ID NOs: 79, 67, and 91) at 24 hours are shown. Figure 21B Cytotoxicity and IL-2 release data of the IMC-2-7 tandem scFv antibody at 24 hours are shown. Figure 21C Cytotoxicity and IL-2 release data of IMC-16-3scFv-Fab IgG antibody at 24 hours are shown. Figure 21D Cytotoxicity and IL-2 release data of IMC-16-15scFv-Fab IgG antibody at 24 hours are shown. Figure 21E Cytotoxicity and IL-2 release data of MC-21-1 antibody at 24 hours are shown. Figure 21F Cytotoxicity and IL-2 release data for IMC-16-7 antibody at 48 hours are shown. Figure 21G Cytotoxicity and IL-2 release data of the IMC-2-7 tandem scFv antibody at 48 hours are shown. Figure 21H Cytotoxicity and IL-2 release data of IMC-16-3scFv-Fab IgG antibody at 48 hours are shown. Figure 21I Cytotoxicity and IL-2 release data of IMC-16-15scFv-Fab IgG antibody at 48 hours are shown. Figure 21J Cytotoxicity and IL-2 release data of IMC-21-1 IgG-(scFv)2 antibody at 48 hours are shown. In each experiment, CKV063 LALA antibody was a negative control.

[0296] Figure 22A , Figure 22B , Figure 22C , Figure 22D , Figure 22E , Figure 22F , Figure 22G , Figure 22H , Figure 22I and Figure 22J is a graph showing cytotoxicity and IL-10 release efficacy data at 24 hours and 48 hours from a cytotoxicity experiment. Figure 22A Cytotoxicity and IL-10 release data of IMC-16-7 antibody at 24 hours are shown. Figure 22B Cytotoxicity and IL-10 release data of IMC-2-7 tandem scFv antibody at 24 hours are shown. Figure 22C Cytotoxicity and IL-10 release data of IMC-16-3scFv-FabIgG antibody at 24 hours are shown. Figure 22D Cytotoxicity and IL-10 release data of IMC-16-15scFv-Fab IgG antibody at 24 hours are shown.Figure 22E Shows the cytotoxicity and IL-10 release data of the IMC-21-1 IgG-(scFv)2 antibody at 24 hours. Figure 22F Shows the cytotoxicity and IL-10 release data of the IMC-16-7 antibody at 48 hours. Figure 22G Shows the cytotoxicity and IL-10 release data of the IMC-2-7 tandem scFv antibody at 48 hours. Figure 22H Shows the cytotoxicity and IL-10 release data of the IMC-16-3 scFv-Fab IgG antibody at 48 hours. Figure 22I Shows the cytotoxicity and IL-10 release data of the IMC-16-15 scFv-Fab IgG antibody at 48 hours. Figure 22J Shows the cytotoxicity and IL-10 release data of the IMC-21-1 IgG-(scFv)2 antibody at 48 hours. In each experiment, the CKV063LALA antibody was the negative control.

[0297] Figure 23A 、 Figure 23B 、 Figure 23C 、 Figure 23D 、 Figure 23E 、 Figure 23F 、 Figure 23G 、 Figure 23H 、 Figure 23I and Figure 23J are graphs showing the cytotoxicity and TNF-α release potency data at 24 hours and 48 hours from the cytotoxicity experiments. Figure 23A Shows the cytotoxicity and TNF-α release data of the IMC-16-7 antibody at 24 hours. Figure 23B Shows the cytotoxicity and TNF-α release data of the IMC-2-7 tandem scFv antibody at 24 hours. Figure 23C Shows the cytotoxicity and TNF-α release data of the IMC-16-3 scFv-Fab IgG antibody at 24 hours. Figure 23D Shows the cytotoxicity and TNF-α release data of the IMC-16-15 scFv-Fab IgG antibody at 24 hours. Figure 23E Shows the cytotoxicity and TNF-α release data of the IMC-21-1 IgG-(scFv)2 antibody at 24 hours. Figure 23F Shows the cytotoxicity and TNF-α release data of the IMC-16-7 antibody at 48 hours. Figure 23G Shows the cytotoxicity and TNF-α release data of the IMC-2-7 tandem scFv antibody at 48 hours. Figure 23HShows the cytotoxicity and TNF-α release data of the IMC-16-3scFv-Fab IgG antibody at 48 hours. Figure 23I Shows the cytotoxicity and TNF-α release data of the IMC-16-15scFv-Fab IgG antibody at 48 hours. Figure 23J Shows the cytotoxicity and TNF-α release data of the IMC-21-1IgG-(scFv)2 antibody at 48 hours. In each experiment, the CKV063LALA antibody was the negative control.

[0298] Figure 24A 、 Figure 24B 、 Figure 24C 、 Figure 24D 、 Figure 24E 、 Figure 24F 、 Figure 24G and Figure 24H are graphs showing cytokine analysis of IFN-γ and IL-2 at 24 hours and 48 hours. Figure 24A Is a graph showing the IFN-γ levels of the IMC-2-7 tandem scFv antibody at 24 hours and 48 hours. Figure 24B Is a graph showing the IFN-γ levels of the IMC-16-3scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 24C Is a graph showing the IFN-γ levels of the IMC-16-15scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 24D Is a graph showing the IFN-γ levels of the IMC-21-1IgG-(scFv)2 antibody at 24 hours and 48 hours. Figure 24E Is a graph showing the IL-2 levels of the IMC-2-7 tandem scFv antibody at 24 hours and 48 hours. Figure 24F Is a graph showing the IL-2 levels of the IMC-16-3scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 24G Is a graph showing the IL-2 levels of the IMC-16-15scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 24H Is a graph showing the IL-2 levels of the IMC-21-1IgG-(scFv)2 antibody at 24 hours and 48 hours.

[0299] Figure 25A 、 Figure 25B 、 Figure 25C 、 Figure 25D 、 Figure 25E 、 Figure 25F 、 Figure 25G 、 Figure 25H 、 Figure 25I and Figure 25JIt is a figure showing the cytokine analysis of IL-10 and TNF-α at 24 hours and 48 hours. Figure 25A It is a figure showing the IL-10 levels of the IMC-16-7 antibody at 24 hours and 48 hours. Figure 25B It is a figure showing the IL-10 levels of the IMC-2-7 tandem scFv antibody at 24 hours and 48 hours. Figure 25C It is a figure showing the IL-10 levels of the IMC-16-3 scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 25D It is a figure showing the IL-10 levels of the IMC-16-15 scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 25E It is a figure showing the IL-10 levels of the IMC-21-1 IgG-(scFv)2 antibody at 24 hours and 48 hours. Figure 25F It is a figure showing the TNF-α levels of the IMC-16-7 antibody at 24 hours and 48 hours. Figure 25G It is a figure showing the TNF-α levels of the IMC-2-7 tandem scFv antibody at 24 hours and 48 hours. Figure 25H It is a figure showing the TNF-α levels of the IMC-16-3 scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 25I It is a figure showing the TNF-α levels of the IMC-16-15 scFv-Fab IgG antibody at 24 hours and 48 hours. Figure 25J It is a figure showing the TNF-α levels of the IMC-21-1 IgG-(scFv)2 antibody at 24 hours and 48 hours.

[0300] Figure 26A and Figure 26B It is a figure showing TNF-α production by human PBMCs co-cultured with HEK cells or OV-90 cells expressing claudin-6. Figure 26AShows the antibody-induced TNF-α levels of IMC-16-13scFv-Fab IgG antibodies (SEQ ID NO: 114, 65, and 80), IMC-16-15scFv-Fab IgG antibodies, IMC-16-3scFv-Fab IgG antibodies, IMC-2-7 tandem scFv antibodies, IMC-2-13 tandem scFv antibodies (SEQ ID NO: 115), IMC-20-13IgG-scFv antibodies (SEQ ID NO: 114, 65, and 116), IMC-21-1IgG-(scFv)2 antibodies, IMC-21-6IgG-(scFv)2 antibodies (SEQ ID NO: 104 and 66), and IMC-2-3 tandem scFv antibodies (SEQ ID NO: 84) in PBMC:HEK-CLDN6 co-cultures. Figure 26B Shows the antibody-induced TNF-α levels of IMC-16-13scFv-Fab IgG antibodies, IMC-16-15scFv-Fab IgG antibodies, IMC-16-3scFv-Fab IgG antibodies, IMC-2-7 tandem scFv antibodies, IMC-2-13 tandem scFv antibodies, IMC-20-13IgG-scFv antibodies, IMC-21-1IgG-(scFv)2 antibodies, IMC-21-6IgG-(scFv)2 antibodies, and IMC-2-3 tandem scFv antibodies in PBMC:OV-90 co-cultures.

[0301] Figure 27A and Figure 27B Is a figure showing that human PBMC co-cultured with HEK cells or OV-90 cells expressing claudin-6 produce IFN-γ. Figure 27A Shows the antibody-induced IFN-γ levels of IMC-16-13scFv-Fab IgG antibodies, IMC-16-15scFv-Fab IgG antibodies, IMC-16-3scFv-Fab IgG antibodies, IMC-2-7 tandem scFv antibodies, IMC-2-13 tandem scFv antibodies, IMC-20-13IgG-scFv antibodies, IMC-21-1IgG-(scFv)2 antibodies, IMC-21-6IgG-(scFv)2 antibodies, and IMC-2-3 tandem scFv antibodies in PBMC:HEK-CLDN6 co-cultures. Figure 27BShows the antibody-induced IFN-γ levels of IMC-16-13scFv-Fab IgG antibody, IMC-16-15scFv-Fab IgG antibody, IMC-16-3scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, IMC-2-13 tandem scFv antibody, IMC-20-13IgG-scFv antibody, IMC-21-1IgG-(scFv)2 antibody, IMC-21-6IgG-(scFv)2 antibody and IMC-2-3 tandem scFv antibody in PBMC:OV-90 co-cultures.

[0302] Figure 28A and Figure 28B is a graph showing the production of IL-2 ( Figure 28A ) and IL-6 levels ( Figure 28B ) by human PBMC co-cultured with OV-90 cells. Figure 28A Shows the antibody-induced IL-2 levels of IMC-16-13scFv-Fab IgG antibody, IMC-16-15scFv-Fab IgG antibody, IMC-16-3scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, IMC-2-13 tandem scFv antibody, IMC-20-13IgG-scFv antibody, IMC-21-1IgG-(scFv)2 antibody, IMC-21-6IgG-(scFv)2 antibody and IMC-2-3 tandem scFv antibody in PBMC:OV-90 co-cultures. Figure 28B Shows the antibody-induced IL-6 levels of IMC-16-13scFv-Fab IgG antibody, IMC-16-15scFv-Fab IgG antibody, IMC-16-3scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, IMC-2-13 tandem scFv antibody, IMC-20-13IgG-scFv antibody, IMC-21-1IgG-(scFv)2 antibody, IMC-21-6IgG-(scFv)2 antibody and IMC-2-3 tandem scFv antibody in PBMC:OV-90 co-cultures.

[0303] Figure 29A 、 Figure 29B 、 Figure 29C and Figure 29D is a graph showing IMC-16-3scFv-Fab IgG antibody ( Figure 29A ), IMC-16-15scFv-Fab IgG antibody ( Figure 29B ), IMC-21-1IgG-(scFv)2 antibody ( Figure 29C) and the binding affinity of the IMC-2-7 tandem scFv antibody to hsCD3δε-biotin Figure 29D ) Graph of the binding affinity for hsCD3δε-biotin.

[0304] Figure 30A and Figure 30B are graphs of cytotoxicity data from a human T cell-dependent cytotoxicity experiment. Figure 30A Shows the cytotoxicity data of the IMC-16-3 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, and negative control (CKV063 LALA) relative to cells expressing K562 CLDN6. Figure 30B Shows the cytotoxicity data of the IMC-16-3 scFv-Fab IgG antibody, IMC-21-1 IgG-(scFv)2 antibody, IMC-16-15 scFv-Fab IgG antibody, IMC-2-7 tandem scFv antibody, and negative control (CKV063 LALA) relative to OV-90 cells.

[0305] Figure 31A and Figure 31B The experiments in show the cytokine analysis data of the IMC-16-3 scFv-Fab IgG antibody ( Figure 31A ) and the IMC-2-7 tandem scFv antibody ( Figure 31B ) of human T cells co-cultured with cells expressing K562 CLDN6. Figure 31A Shows the TNF-α expression level of human T cells co-cultured with cells expressing K562 CLDN6, and Figure 31B shows the IFN-γ expression level of human T cells co-cultured with cells expressing K562 CLDN6.

[0306] Figure 32 Is a non-limiting image showing the key residues bound by monoclonal antibodies identified using a CLDN6 alanine scan library expressed in HEK-293T cells. CLDN6 specificity was determined by identifying the Q156 γ-carbon ( Figure 4 ). In CLDN9, the native L156 residue causes steric hindrance to monoclonal antibody binding.

[0307] Figure 33A and Figure 33B Are graphs showing that the binding of the IMC-16-3 scFv-Fab IgG antibody is highly specific for CLDN6. Figure 33AShows the binding data of IMC-16-3scFv-Fab IgG antibody, IMC-16-15scFv-Fab IgG antibody, IMC-21-1IgG-(scFv)2 antibody and IMC-2-7 tandem scFv antibody to HEK293-F cells transiently expressing CLDN6. Figure 33B Shows the binding data of IMC-16-3scFv-Fab IgG antibody, IMC-16-15scFv-Fab IgG antibody, IMC-21-1IgG-(scFv)2 antibody and IMC-2-7 tandem scFv antibody to HEK293-F cells transiently expressing CLDN9.

[0308] Figure 34 Is a graph showing the specific cytotoxicity mediated by the IMC-16-3scFv-Fab IgG antibody, which is strongly preferential for CLDN6.

[0309] Figure 35A and Figure 35B Is a graph showing the activation of CD4 ( Figure 35B ) and CD8 ( Figure 35A ) T cells by the bispecific antibody IMC-16-3 in the presence of tumor cells expressing CLDN-6, as indicated by the expression of activation markers CD69 and CD25 on human cytotoxic T cells (Tc) and human helper cells (Th).

[0310] Figure 36 Shows the results of a preclinical animal study of OV-90 xenografts treated with a physiologically relevant dose of IMC-16-3.

[0311] Figure 37A and Figure 37B Shows the selectivity of a reference antibody (RefMAB#1, Figure 37A ) and IMC-16-3 ( Figure 37B ) for various tight junction proteins.

[0312] Figure 38A and Figure 38B Shows the results of the internalization assessment of IMC-16-3 and RefMAB#2. Figure 38A Shows the percentage of internalization of the antibody in the K562 cell line with high CLDN6 expression. Figure 38B Shows the percentage of internalization of the antibody in OV-90 cells with moderate CLDN6 expression.

[0313] Figure 39A Shows the results of an OVCAR3 xenograft tumor study in mice treated with various concentrations of IMC-16-3.

[0314] Figure 39B shows the body weight of the mice over the entire duration of the Figure 39A study.

[0315] Figure 40 shows the plasma levels of IMC-16-3 in the plasma of non-human

[0316] Figure 41A , Figure 41B and Figure 41C shows the comparative selectivity of RefMAB#2 ( Figure 41A ), RefMAB#3 ( Figure 41B ) and IMC-16-3 ( Figure 41C ) for various tight junction proteins.

[0317] Figure 42A and Figure 42B shows the results of a comparative T cell-dependent Figure 42A cytotoxicity assay comparing IMC-16-3 and RefMAB#3. Figure 42B shows the results when a 12.5:1 E:T ratio was used.

[0318] Figure 43A , Figure 43B , Figure 43C and Figure 43D shows the results of a comparative PBMC cytokine production Figure 43A assay comparing IMC-16-3 and RefMAB#3. Figure 43B shows IL-6 production. Figure 43C shows IL-2 production. Figure 43D shows TNF-α production.

[0319] Figure 44A , Figure 44B and Figure 44C shows the results of a comparative K562-CLDN6 killing Figure 44A assay comparing IMC-16-3 and RefMAB#2 in cell lines with Figure 44B different CLDN6 expression levels and in the presence or Figure 44C absence of human PBMC.

[0320] Figure 45Shows the pharmacokinetic results of IMC-16-3 in non-human primates dosed with 0.1 mg / kg or 1 mg / kg IMC-16-3. Detailed Description

[0321] This disclosure is in part based on the surprising discovery of antibodies specific for claudin 6 and CD3. This disclosure describes the isolation and characterization of antibodies, antibody fragments, and antibody variants specific for claudin 6 and CD3. In some embodiments, the antibody specific for claudin 6 and CD3 is a tandem single-chain variable fragment (scFv). In some embodiments, the antibody specific for claudin 6 and CD3 is an scFv-Fab Fc antibody specific for claudin 6 and CD3. In some embodiments, the antibody specific for claudin 6 and CD3 is an IgG-(scFV)2 antibody specific for claudin 6 and CD3. In some embodiments, the antibody specific for claudin 6 and CD3 is an scFv-Fab Fc specific for claudin 6 and CD3. In some embodiments, the antibody specific for claudin 6 and CD3 binds both claudin 6 and CD3 simultaneously.

[0322] For example, in some embodiments, the antibody specific for claudin 6 and CD3 is a tandem scFv selected from the amino acid sequences of SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ IDNO:99, SEQ ID NO:100, SEQ ID NO:109, SEQ ID NO:110, or 115, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0323] In some embodiments, the antibody specific for claudin 6 and CD3 is a scFv-Fab Fc antibody comprising a first heavy chain sequence, a second heavy chain sequence, and a light chain sequence. For example, the antibody specific for claudin 6 and CD3 is selected from a first heavy chain having the amino acid sequence of SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, a second heavy chain having the amino acid sequence of SEQ ID NO:80, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:111, or SEQ ID NO:116, and a light chain having the amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66. In some embodiments, the first heavy chain comprises the amino acid sequence of SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the second heavy chain comprises the amino acid sequence of SEQ ID NO:80, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:111, or SEQ ID NO:116, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the light chain comprises the amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0324] In some embodiments, the antibody specific for claudin 6 and CD3 is an IgG-(scFV)2 antibody comprising a heavy chain selected from the amino acid sequences of SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:112 or SEQ ID NO:113, and a light chain selected from the amino acid sequences of SEQ ID NO:67, SEQ ID NO:65 or SEQ ID NO:66. In some embodiments, the heavy chain comprises the amino acid sequence of SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:112 or SEQ ID NO:113, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the light chain comprises the amino acid sequence of SEQ ID NO:67, SEQ ID NO:65 or SEQ ID NO:66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0325] In some embodiments, the antibody specific for claudin 6 and CD3 is a scFv-Fab Fc antibody that comprises a first heavy chain having an amino acid sequence selected from SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, a second heavy chain having an amino acid sequence selected from SEQ ID NO:81, and a light chain having an amino acid sequence selected from SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66. In some embodiments, the antibody comprises the first heavy chain amino acid sequence of SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises the second heavy chain amino acid sequence of SEQ ID NO:81, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises the light chain amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0326] In some embodiments, the antibody specific for claudin 6 and CD3 is a scFv-Fab Fc antibody that comprises a first heavy chain having an amino acid sequence selected from SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, a second heavy chain having an amino acid sequence selected from SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:118, or SEQ ID NO:120, and a light chain having an amino acid sequence selected from SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66. In some embodiments, the antibody comprises the first heavy chain amino acid sequence of SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises the second heavy chain amino acid sequence of SEQ ID NO:117, SEQ ID NO:119, SEQ ID NO:118, or SEQ ID NO:120, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises the light chain amino acid sequence of SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0327] In some embodiments, the antibody specific for claudin 6 and CD3 is a scFv-Fab Fc antibody that comprises a first heavy chain having an amino acid sequence selected from SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88, a second heavy chain having an amino acid sequence selected from SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129, a first light chain having an amino acid sequence selected from SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66, and a second light chain having an amino acid sequence selected from SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, or SEQ ID NO:130. In some embodiments, the antibody comprises a first heavy chain having an amino acid sequence selected from SEQ ID NO:79, SEQ ID NO:114, or SEQ ID NO:88 or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a second heavy chain having an amino acid sequence selected from SEQ ID NO:121, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:127, SEQ ID NO:129 or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a first light chain having an amino acid sequence selected from SEQ ID NO:67, SEQ ID NO:65, or SEQ ID NO:66 or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto. In some embodiments, the antibody comprises a second light chain having an amino acid sequence selected from SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:126, SEQ ID NO:128, or SEQ ID NO:130 or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0328] In various embodiments, an antibody (e.g., tandem scFv antibody, scFv-Fab Fc antibody, IgG-(scFV)2 antibody, and scFv-Fab Fc antibody) or a fragment or variant thereof may comprise an amino acid sequence having one or more amino acid mutations (e.g., substitutions or deletions) relative to any sequence disclosed herein. In some embodiments, one or more amino acid mutations may independently be selected from substitutions, insertions, deletions, and truncations. In an embodiment, an antibody (e.g., tandem scFv antibody, scFv-Fab Fc antibody, IgG-(scFV)2 antibody, and scFv-Fab Fc antibody) or a fragment or variant thereof comprises a sequence having about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid mutations relative to any of the amino acid sequences disclosed herein.

[0329] In various embodiments, an antibody or antibody format (e.g., tandem scFv antibody, scFv-Fab Fc antibody, IgG-(scFV)2 antibody, and scFv-Fab Fc antibody) or a fragment or variant thereof may comprise an amino acid sequence having at least about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% sequence homology to an amino acid sequence disclosed herein.

[0330] In various embodiments, variants or fragments are disclosed herein that comprise any of the sequences described herein, e.g., sequences having at least about 60%, or at least about 61%, or at least about 62%, or at least about 63%, or at least about 64%, or at least about 65%, or at least about 66%, or at least about 67%, or at least about 68%, or at least about 69%, or at least about 70%, or at least about 71%, or at least about 72%, or at least about 73%, or at least about 74%, or at least about 75%, or at least about 76%, or at least about 77%, or at least about 78%, or at least about 79%, or at least about 80%, or at least about 81%, or at least about 82%, or at least about 83%, or at least about 84%, or at least about 85%, or at least about 86%, or at least about 87%, or at least about 88%, or at least about 89%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99% sequence identity to any sequence disclosed herein.

[0331] In some embodiments, variants are those that have conservative amino acid substitutions at one or more predicted non-essential amino acid residues. For example, a "conservative amino acid substitution" is a substitution in which an amino acid residue is replaced with an amino acid residue having a similar side chain.

[0332] In embodiments, the amino acid mutation is an amino acid substitution and can include conservative substitutions and / or non-conservative substitutions. Throughout the present disclosure, when the context permits, the terms "mutation" and "substitution" are used interchangeably. For example, the substitution of threonine at position 366 of a protein with serine can be referred to as a T366S substitution or a T366S mutation. Those skilled in the art will readily understand that "T366S" means that serine substitutes for threonine at position 366, and thus those skilled in the art will readily understand that a "T366S mutation" refers to a substitution.

[0333] "Conservative substitutions" can be made, for example, based on the similarity of the amino acid residues involved in terms of polarity, charge, size, solubility, hydrophobicity, hydrophilicity, and / or amphipathic nature. The 20 naturally occurring amino acids can be grouped into the following six standard amino acid groups: (1) hydrophobic: Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser, Thr; Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues affecting chain orientation: Gly, Pro; and (6) aromatic: Trp, Tyr, Phe.

[0334] As used herein, "conservative substitution" is defined as an amino acid being exchanged for another amino acid listed in the same group among the six standard amino acid groups shown above. For example, the exchange of Asp for Glu retains a negative charge in the polypeptide so modified. Additionally, based on the ability of glycine and proline to disrupt α-helices, they can substitute for each other.

[0335] As used herein, "non-conservative substitution" is defined as an amino acid being exchanged for another amino acid listed in a different group among the six standard amino acid groups (1) to (6) shown above.

[0336] As disclosed herein, the term "antibody" is used in a broad sense and includes immunoglobulin or antibody molecules, including polyclonal antibodies, monoclonal antibodies (including murine, human, humanized, and chimeric monoclonal antibodies), and antibody fragments, such as ScFv (PLOS Biology | DOI: 10.1371 / journal.pbio.1002344 January 6, 2016, the entire text of which is incorporated herein by reference).

[0337] Generally speaking, an antibody is a protein or polypeptide that exhibits binding specificity for a specific antigen. A complete antibody is a heterotetrameric glycoprotein composed of two identical light chains and two identical heavy chains. Typically, each light chain is linked to a heavy chain by a covalent disulfide bond, and the number of disulfide bonds varies between the heavy chains of different immunoglobulin isotypes. Each heavy chain and light chain also has regularly spaced intra-chain disulfide bridges. Each heavy chain has a variable domain (VH) at one end, followed by multiple constant domains. Each light chain has a variable domain (VL) at one end and a constant domain at the other end; the constant domain of the light chain aligns with the first constant domain of the heavy chain, and the variable domain of the light chain aligns with the variable domain of the heavy chain. The antibody light chains of any vertebrate species can be designated as one of two distinct types based on the amino acid sequence of their constant domains, namely κ and λ. According to the amino acid sequence of the heavy chain constant domain, immunoglobulins can be divided into five major classes, namely IgA, IgD, IgE, IgG, and IgM. IgA and IgG are further subdivided into isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4.

[0338] As disclosed herein, the term "antibody fragment" refers to a complete antibody, typically the antigen-binding region or variable region of a complete antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments, diabodies, single-chain antibody molecules, and multispecific antibodies formed by at least two complete antibodies or their fragments.

[0339] As disclosed herein, the term "antigen" refers to any molecule that has the ability to directly or indirectly generate an antibody.

[0340] As disclosed herein, the term "specifically binds" or "immunologically specifically binds" or "immunologically specifically binds to" means that an antibody binds to a predetermined antigen (e.g., claudin 6) or an epitope present on the antigen. In some embodiments, the antibody binds with an affinity of about 10 -10 M or less, about 10 -9 M or less, about 10 -8 M or less, about 10 -7 M or less, about 10 -6 M or less, about 10 -5binds with a dissociation constant (KD) of M or less and binds the predetermined antigen with a KD that is at most 1 / 2 of the KD with which it binds a non-specific antigen other than the predetermined antigen (e.g., BSA, casein, or another non-specific polypeptide). The phrases “antibody that recognizes claudin-6” and “antibody specific for claudin-6” are used interchangeably herein with the term “antibody that immunospecifically binds claudin-6”. Claudin-6 may be referenced in the present disclosure. In some embodiments, the antibody is specific for claudin-6 and does not specifically bind claudin-3, claudin-4, and / or claudin-9.

[0341] “CDR” refers to the amino acid sequences of the complementarity determining regions of an antibody, which are the hypervariable regions of the immunoglobulin heavy and light chains. See, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 4th Ed., U.S. Department of Health and Human Services, National Institutes of Health (1987). There are three heavy chain and three light chain CDRs or CDR regions in the variable portion of an immunoglobulin. Thus, as used herein, “CDR” refers to all three heavy chain CDRs, or all three light chain CDRs, or both all heavy chain CDRs and all light chain CDRs (where appropriate).

[0342] Each variable region contains three hypervariable regions, also known as complementarity determining regions (CDRs), flanked by four relatively conserved framework regions (FRs). The three CDRs, designated CDR1, CDR2, and CDR3, contribute to antibody binding specificity because the CDRs provide most of the contact residues by which the antibody binds an antigen or epitope. The CDRs of interest may be derived from donor antibody variable heavy and light chain sequences and include analogs of naturally occurring CDRs that also share or retain the same antigen binding specificity and / or neutralizing capacity as the donor antibody from which they are derived. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody.

[0343] CDRs are sequence-variable (Wu and Kabat, J. Exp. Med. 132:211-250, 1970). There are six CDRs - three in the variable heavy chain or VH and commonly named H-CDR1, H-CDR2, and H-CDR3, and three in the variable light chain or VL and commonly named L-CDR1, L-CDR2, and L-CDR3 (Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, Md., 1991). "Hypervariable region", "HVR", or "HV" refers to the structurally variable regions in the antibody variable domain as defined by Chothia and Lesk (Chothia and Lesk, Mol. Biol. 196:901-917, 1987). There are six HVRs, three in VH (H1, H2, H3), and three in VL (L1, L2, L3). Chothia and Lesk referred to the structurally conserved HVs as "canonical structures". Lefranc proposed another method for describing the regions forming the antigen-binding site based on a comparison of the V domains from immunoglobulins and T cell receptors (Lefranc et al., Developmental & Comparative Immunology 27:55-77, 2003). According to Almagro (Almagro, Mol. Recognit. 17:132-43, 2004), the antigen-binding site can also be delineated based on "specificity-determining residue usage (SDRU)", where SDRU refers to the amino acid residues of an immunoglobulin that are directly involved in antigen contact.

[0344] As used herein, an "isolated antibody" refers to an antibody that is substantially free of other antibodies having different antigen specificities (e.g., an isolated antibody that specifically binds claudin 6 is substantially free of antibodies that specifically bind antigens other than claudin 6). In addition, an isolated antibody can be substantially free of other cellular materials and / or chemicals. An isolated antibody can also be sterile or pyrogen-free or formulated as an injectable pharmaceutical as described herein.

[0345] In some embodiments, the source of DNA encoding a non-human antibody includes cell lines that produce antibodies, such as hybrid cell lines commonly known as hybridomas.

[0346] Claudin 6 / CD3 conjugate

[0347] In some embodiments, an antibody specific for claudin 6 and CD3 (e.g., tandem scFv antibody, scFv-Fab Fc antibody, IgG-(scFV)2 antibody, and scFv-Fab Fc antibody) or a fragment or variant thereof is selected from one of the following amino acid sequences. Bold refers to the CDR based on the Kabat name, and the underlined format refers to the linker.

[0348]

[0349]

[0350]

[0351]

[0352]

[0353]

[0354]

[0355]

[0356]

[0357]

[0358]

[0359] >SEQ ID NO:116

[0360] EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSSGGGGSGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSMGSGVSWSGYVATSIDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:116)

[0361]

[0362]

[0363]

[0364]

[0365]

[0366]

[0367]

[0368]

[0369]

[0370]

[0371]

[0372]

[0373]

[0374]

[0375] >SEQ ID NO:117

[0376] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDAWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGTGGGGSEVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSS(SEQID NO:117)

[0377] >SEQ ID NO:119

[0378] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGTGGGGSEVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSS(SEQ ID NO:119)

[0379] >SEQ ID NO:118

[0380] EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSSGGGGSGGGGTGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDAWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:118)

[0381] >SEQ ID NO:120

[0382] EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSSGGGGSGGGGTGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:120)

[0383] In some embodiments, an antibody (e.g., tandem scFv antibody, scFv-Fab Fc antibody, IgG-(scFV)2 antibody, and scFv-Fab Fc antibody) or a fragment or a variant thereof that is specific for claudin 6 and CD3 is selected from one of the following amino acid sequences:

[0384] >CH-HAMF5-1HEP-VH(SEQ ID NO:69)

[0385] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDAWGQGTLVTVSS(SEQ ID NO:69)

[0386] >CH-HAMF5-1HEP-VL(SEQ ID NO:68)

[0387] SYELTQPPSVSVSPGQTARITCSAGSGLYGWYQQKPGQAPVLVIYGTNKRPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCGSADSSTNAGIFGGGTKLTVL(SEQ ID NO:68)

[0388] >CD3 linker (SEQ ID NO:75)

[0389] EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSS(SEQ ID NO:75)

[0390] In some embodiments, the antibodies (such as tandem scFv antibodies, scFv-FabFc antibodies, IgG-(scFV)2 antibodies, and scFv-FabFc antibodies), fragments, or variants thereof that are specific for claudin 6 and CD3 are selected from one of the following amino acid sequences:

[0391] >CH-HAMF5-1HEP-HC(SEQ ID NO:76)

[0392] EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMNWVRQAPGKGLEWVAGISSSGRYTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKSVGSGVSWSGYVATSLDAWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:76)

[0393] >CH-HAMF5-1HEP-LC(SEQ ID NO:77)

[0394] SYELTQPPSVSVSPGQTARITCSAGSGLYGWYQQKPGQAPVLVIYGTNKRPSGIPERFSGSSSGTTVTLTISGVQAEDEADYYCGSADSSTNAGIFGGGTKLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS(SEQ IDNO:77)

[0395] >3983-HC(SEQ ID NO:78)

[0396] EVQLVESGGGPVQAGGSLRLSCAASGRTYRGYSMGWFRQAPGKEREFVAAIVWSGGNTYYEDSVKGRFTISRDNAKNTMYLQMTSLKPEDSATYYCAAKIRPYIFKIAGQYDYWGQGTQVTVSSASPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:78)

[0397] In some embodiments, the antibodies or antibody fragments or variants disclosed herein (e.g., tandem scFv antibodies, scFv-Fab Fc antibodies, IgG-(scFv)2 antibodies, and scFv-Fab Fc antibodies) comprise a CD3 linker. In some embodiments, the CD3 linker is selected from muOKT3, huOKT3, huSP34, huUCHT1, and CD3 nanobody (VHH).

[0398] In some embodiments, the antibodies or antibody fragments or variants disclosed herein (e.g., tandem scFv antibodies, scFv-Fab Fc antibodies, IgG-(scFv)2 antibodies, and scFv-Fab Fc antibodies) comprise a linker having one or more glycines and serines replaced by their functionally equivalent variants. In some embodiments, the linker is identified by the underlined text above. For example, in some embodiments, the linker is selected from the amino acid sequences of GGGGSGGGGSGGGGS (SEQ ID NO:50), GGGGS (SEQ ID NO:51), GGSGGSGGSGGSGGVD (SEQ ID NO:52), and GKPGSGKPGSGKPGSGKPGS (SEQ ID NO:53).

[0399] In some embodiments, the linker may be derived from a naturally occurring multidomain protein or an empirical linker as described, for example, in Chichili et al., (2013), Protein Sci. 22(2):153-167; Chen et al., (2013), Adv Drug Deliv Rev. 65(10):1357-1369, the entire contents of which are incorporated herein by reference. In some embodiments, the linker may be designed using linker design databases and computer programs as described, for example, in Chen et al., (2013), Adv Drug Deliv Rev. 65(10):1357-1369 and Crasto et al., (2000), Protein Eng. 13(5):309-312, the entire contents of which are incorporated herein by reference.

[0400] In some embodiments, the linker is a polypeptide. In some embodiments, the linker length is less than about 100 amino acids. For example, the linker length may be less than about 100, about 95, about 90, about 85, about 80, about 75, about 70, about 65, about 60, about 55, about 50, about 45, about 40, about 35, about 30, about 25, about 20, about 19, about 18, about 17, about 16, about 15, about 14, about 13, about 12, about 11, about 10, about 9, about 8, about 7, about 6, about 5, about 4, about 3, or about 2 amino acids. In some embodiments, the linker is flexible. In another embodiment, the linker is rigid. In various embodiments, the linker consists substantially of glycine and serine residues (e.g., about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 90%, or about 95%, or about 97% glycine and serine).

[0401] Additional exemplary linkers include, but are not limited to, those having the sequences LE, GGGGS (SEQ ID NO:51), (GGGGS) n (n = 1-4) (SEQ ID NO:54), (Gly)8 (SEQ ID NO:55), (Gly)6 (SEQ ID NO:56), (EAAAK) n (n = 1-3) (SEQ ID NO:57), A(EAAAK) nA (n = 2 - 5) (SEQ ID NO:58), AEAAAKEAAAKA (SEQ ID NO:59), A(EAAAK)4ALEA(EAAAK)4A (SEQ ID NO:60), PAPAP(SEQ ID NO:61), KESGSVSSEQLAQFRSLD(SEQ ID NO:62), EGKSSGSGSESKST(SEQ ID NO:63), GSAGSAAGSGEF(SEQ ID NO:64), and (XP) n a linker of (n = 1 - 5) (SEQ ID NO:131), where X represents any amino acid, such as Ala, Lys, or Glu.

[0402] In various embodiments, the linker can be functional. For example but not limited to, the linker can be used to improve the folding and / or stability of the compositions of the present invention, improve expression, improve pharmacokinetics, and / or improve biological activity. In another example, the linker can serve to target the composition to a specific cell type or location.

[0403] In some embodiments, a composition is disclosed herein that comprises a tandem single-chain variable fragment (scFv) specific for claudin 6 and CD3, the composition comprising one or more of the following:

[0404] I.

[0405] (a) the amino acid sequence of SEQ ID NO.82, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0406] (b)

[0407] (i) a light chain variable region (VL) comprising LCDR1, LCDR2, and LCDR3 sequences, where the LCDR1 comprises the amino acid sequence of SAGSGLYG (SEQ ID NO:1) or a variant thereof, the LCDR2 sequence comprises the amino acid sequence of GTNKRPS (SEQ ID NO:2) or a variant thereof, and the LCDR3 sequence comprises the amino acid sequence of GSADSSTNAGI (SEQ ID NO:3) or a variant thereof,

[0408] (ii) A variable heavy chain (VH) comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SYAMN (SEQ ID NO:4) or a variant thereof, said HCDR2 comprises the amino acid sequence of GISSSGRYTGYADSVKG (SEQ ID NO:5) or a variant thereof, and said HCDR3 comprises the amino acid sequence of SVGSGVSWSGYVA TSLDA (SEQ ID NO:6) or a variant thereof,

[0409] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of RYTMH (SEQ ID NO:7) or a variant thereof, said HCDR2 comprises the amino acid sequence of YINPSRGYTNYNQKFKD (SEQ ID NO:8) or a variant thereof, and said HCDR3 comprises the amino acid sequence of YYDDHYCLDY (SEQ ID NO:9) or a variant thereof, and

[0410] (iv) A variable light chain (VL) comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of RASSSVSYMN (SEQ ID NO:10) or a variant thereof, said LCDR2 comprises the amino acid sequence of DTSKVAS (SEQ ID NO:11) or a variant thereof, and said LCDR3 comprises the amino acid sequence of QQWSSNPLT (SEQ ID NO:12) or a variant thereof,

[0411] II.

[0412] (a) The amino acid sequence of SEQ ID NO.83, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto,

[0413] Or

[0414] (b)

[0415] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SGGSGSYG (SEQ ID NO:13) or a variant thereof, said LCDR2 comprises the amino acid sequence of GTYKRPS (SEQ ID NO:14) or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0416] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SVGSGVSWSGYVATSLDV (SEQ ID NO:15) or a variant thereof,

[0417] (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:8 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0418] (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:10 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:11 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:12 or a variant thereof,

[0419] III.

[0420] (a) the amino acid sequence of SEQ ID NO.84, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0421] (b)

[0422] (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0423] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the sequence of SEQ ID NO:6 or a variant thereof, and

[0424] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of GYSMG (SEQ ID NO:16) or a variant thereof, said HCDR2 comprises the amino acid sequence of AIVWSGGNTYYEDSVKG (SEQ ID NO:17) or a variant thereof, and said HCDR3 comprises the amino acid sequence of KIRPYIFKIAGQYDY (SEQ ID NO:18) or a variant thereof,

[0425] IV.

[0426] (a) The amino acid sequence of SEQ ID NO:85, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0427] (b)

[0428] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0429] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, and

[0430] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0431] V.

[0432] (a) The amino acid sequence of SEQ ID NO.93, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0433] (b)

[0434] (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0435] (ii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0436] (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of KYAMN (SEQ ID NO:19) or a variant thereof, said HCDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKD (SEQ ID NO:20) or a variant thereof, and said HCDR3 comprises the amino acid sequence of HGNFGNSYISYWAY (SEQ ID NO:21) or a variant thereof, and

[0437] (iv) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of GSSTGAVTSGNYPN (SEQ ID NO:22) or a variant thereof, said LCDR2 comprises the amino acid sequence of GTKFLAP (SEQ ID NO:23) or a variant thereof, and said LCDR3 comprises the amino acid sequence of VLWYSNRWV (SEQ ID NO:24) or a variant thereof,

[0438] VI.

[0439] (a) The amino acid sequence of SEQ ID NO.94, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0440] (b)

[0441] (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0442] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0443] (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, and

[0444] (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof,

[0445] VII.

[0446] (a) the amino acid sequence of SEQ ID NO.95, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0447] (b)

[0448] (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0449] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0450] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of TYAMN (SEQ ID NO:25) or a variant thereof, said HCDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKG (SEQ ID NO:26) or a variant thereof, and said HCDR3 comprises the amino acid sequence of HGNFGDSYVSWFAY (SEQ ID NO:27) or a variant thereof, and

[0451] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of GSSTGAVTTSNYAN (SEQ ID NO:28) or a variant thereof, said LCDR2 comprises the amino acid sequence of GTNKRAP (SEQ ID NO:29) or a variant thereof, and said LCDR3 comprises the amino acid sequence of ALWYSNHWV (SEQ ID NO:30) or a variant thereof,

[0452] VIII.

[0453] (a) The amino acid sequence of SEQ ID NO.96, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0454] (b)

[0455] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0456] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0457] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, and

[0458] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof,

[0459] IX.

[0460] (a) The amino acid sequence of SEQ ID NO. 97, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0461] (b)

[0462] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0463] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[0464] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of RIRSKYNNYATYYADSVKS (SEQ ID NO: 31) or a variant thereof, and the HCDR3 comprises the amino acid sequence of HGNFGNSYVSWFAY (SEQ ID NO: 32) or a variant thereof, and

[0465] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of RSSTGAVTTSNYAN (SEQ ID NO: 33) or a variant thereof, the LCDR2 comprises the amino acid sequence of GANKRAP (SEQ ID NO: 34) or a variant thereof, and the LCDR3 comprises the amino acid sequence of ALWYSNLWV (SEQ ID NO: 35) or a variant thereof,

[0466] X.

[0467] (a) The amino acid sequence of SEQ ID NO.98, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0468] (b)

[0469] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0470] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0471] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, and

[0472] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof,

[0473] XI.

[0474] (a) The amino acid sequence of SEQ ID NO.99, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0475] (b)

[0476] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0477] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0478] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of YINPSRGYTNYNQKVKD (SEQ ID NO:36) or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0479] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SASSSVSYMN (SEQ ID NO:37) or a variant thereof, said LCDR2 comprises the amino acid sequence of DTSKLAS (SEQ ID NO:38) or a variant thereof, and said LCDR3 comprises the amino acid sequence of QQWSSNPFT (SEQ ID NO:39) or a variant thereof,

[0480] XII.

[0481] (a) The amino acid sequence of SEQ ID NO.100, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0482] (b)

[0483] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0484] (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0485] (iii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0486] (iv) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof,

[0487] XIII.

[0488] (a) the amino acid sequence of SEQ ID NO:109, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0489] (b)

[0490] (i) a VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0491] (ii) a VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0492] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of GYTMN (SEQ ID NO: 40) or a variant thereof, the HCDR2 comprises the amino acid sequence of LINPYKGVSTYNQKVKG (SEQ ID NO: 41) or a variant thereof, and the HCDR3 comprises the amino acid sequence of SGYYGDSDWYFDV (SEQ ID NO: 42) or a variant thereof, and

[0493] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of RASQDIRNYLN (SEQ ID NO: 43) or a variant thereof, the LCDR2 comprises the amino acid sequence of YTSRLHS (SEQ ID NO: 44) or a variant thereof, and the LCDR3 comprises the amino acid sequence of QQGNTLPWT (SEQ ID NO: 45) or a variant thereof, and

[0494] XIV.

[0495] (a) The amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0496] (b)

[0497] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0498] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[0499] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof, and

[0500] (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof, or

[0501] wherein:

[0502] any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N-terminus or C-terminus, and

[0503] any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0504] In some embodiments, antibodies such as tandem scFv antibodies specific for claudin 6 and CD3 comprise the CDR sequences shown in Table 1 below:

[0505]

[0506]

[0507]

[0508]

[0509] In some embodiments, a composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3 is disclosed herein, and the antibody comprises:

[0510] (a) a first heavy chain selected from:

[0511] (i) SEQ ID NO: 79,

[0512] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0513] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[0514] (ii) SEQ ID NO:88,

[0515] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0516] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or

[0517] (iii) SEQ ID NO:114,

[0518] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0519] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SMGSGVSWSGYVATSIDV (SEQ ID NO:47) or a variant thereof,

[0520] (b) A second heavy chain, the second heavy chain selected from:

[0521] (i.) SEQ ID NO:80,

[0522] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0523] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, or

[0524] (ii.) SEQ ID NO:89,

[0525] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0526] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, or

[0527] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, or

[0528] (iii.) SEQ ID NO: 90,

[0529] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0530] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof, or

[0531] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of RSSTGAVTTSNYA (SEQ ID NO: 48) or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof, or

[0532] (iv.) SEQ ID NO: 91,

[0533] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0534] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof, or

[0535] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of GSSTGAVTSGNYP (SEQ ID NO: 49) or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof, or

[0536] (v.) SEQ ID NO: 92,

[0537] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0538] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof, or

[0539] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof, or

[0540] (vi.) SEQ ID NO: 111,

[0541] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0542] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof, or

[0543] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof; and

[0544] (c) A first light chain, wherein the first light chain is selected from:

[0545] (i) SEQ ID NO: 67,

[0546] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0547] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0548] (ii) SEQ ID NO: 66,

[0549] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0550] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, or

[0551] (iii) SEQ ID NO: 65,

[0552] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0553] a light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0554] wherein:

[0555] any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0556] any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0557] In some embodiments, the Fc is from IgG.

[0558] In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3 and IgG4.

[0559] In some embodiments, the antibody is formed by a knob-in-hole interaction in the Fc region. In some embodiments, the human IgG Fc contains one or more mutations to facilitate the knob-in-hole interaction. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A or Y407V. In some embodiments, the mutations are selected from:

[0560] (a) T366Y and Y407T in human IgG1 or T366Y / F405A and T394W / Y407T, or

[0561] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0562] T366W / K392C and T366S / L368A / D399C / Y407V;

[0563] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0564] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0565] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0566] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0567] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0568] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0569] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1.

[0570] In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0571] In some embodiments, the scFv-Fab antibody specific for claudin 6 and CD3 comprises the CDR sequences shown in Table 2 below:

[0572] Table 2: Exemplary scFv-Fab Sequences

[0573]

[0574]

[0575] In some embodiments, the scFv-Fab antibody specific for claudin 6 and CD3 comprises the CDR sequences shown in Table 3 below:

[0576] Table 3: Exemplary scFv-Fab Sequences

[0577]

[0578]

[0579]

[0580] In some embodiments, the scFv-Fab antibody specific for claudin 6 and CD3 comprises the CDR sequences shown in Table 4 below:

[0581] Table 4: Exemplary scFv-Fab antibodies

[0582]

[0583]

[0584] In some embodiments, a composition is disclosed herein that comprises an IgG-(scFV)2 antibody that is specific for claudin 6 and CD3, the antibody comprising:

[0585] (a) a heavy chain selected from:

[0586] (i.) SEQ ID NO:86,

[0587] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0588] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[0589] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0590] (ii.) SEQ ID NO:87,

[0591] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0592] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or

[0593] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0594] (iii.) SEQ ID NO: 101,

[0595] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0596] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[0597] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof, or

[0598] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof,

[0599] (iv.) SEQ ID NO: 102,

[0600] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0601] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[0602] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, or

[0603] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof,

[0604] (v.) SEQ ID NO:103,

[0605] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0606] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[0607] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, or

[0608] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof,

[0609] (vi.) SEQ ID NO:104,

[0610] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0611] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or

[0612] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, or

[0613] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof,

[0614] (vii.) SEQ ID NO:105,

[0615] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0616] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[0617] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, or

[0618] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof,

[0619] (viii.) SEQ ID NO: 106,

[0620] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0621] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[0622] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof, or

[0623] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof,

[0624] (ix.) SEQ ID NO: 107,

[0625] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0626] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[0627] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof, or

[0628] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof,

[0629] (x.) SEQ ID NO: 108,

[0630] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0631] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[0632] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof, or

[0633] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof,

[0634] (xi.) SEQ ID NO: 112,

[0635] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0636] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[0637] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, or

[0638] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof,

[0639] (xii.) SEQ ID NO:113,

[0640] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0641] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or

[0642] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, or

[0643] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof;

[0644] and

[0645] (b) A light chain selected from:

[0646] (i) SEQ ID NO: 67,

[0647] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0648] a light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0649] (ii) SEQ ID NO: 66,

[0650] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0651] a light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0652] or

[0653] (iii) SEQ ID NO: 65,

[0654] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0655] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[0656] wherein:

[0657] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0658] Any of the above sequences optionally has a linker comprising one or more glycines and serines, and said linker is replaced by another peptide linker or a functionally equivalent variant thereof.

[0659] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0660] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutation is the L234A and L235A (LALA) substitution in human IgG1.

[0661] In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0662] In some embodiments, the IgG-(scFv)2 antibody specific for claudin 6 and CD3 comprises the CDR sequences shown in Table 5 below:

[0663]

[0664]

[0665]

[0666] In some embodiments, a composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3 is disclosed herein, said antibody comprising:

[0667] (a) A first heavy chain, said first heavy chain selected from:

[0668] (i) SEQ ID NO:79,

[0669] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0670] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0671] (ii) SEQ ID NO:88,

[0672] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0673] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0674] Or

[0675] (iii) SEQ ID NO:114,

[0676] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0677] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof,

[0678] (b) A second heavy chain, the second heavy chain selected from:

[0679] SEQ ID NO:81,

[0680] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0681] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0682] and

[0683] (c) A light chain selected from:

[0684] (i) SEQ ID NO: 67,

[0685] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0686] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0687] (ii) SEQ ID NO: 66

[0688] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0689] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0690] or

[0691] (iii) SEQ ID NO: 65,

[0692] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0693] A light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[0694] wherein:

[0695] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0696] Any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0697] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3 and IgG4.

[0698] In some embodiments, the antibody is formed by a knob-in-hole interaction in the Fc region. In some embodiments, the human IgG Fc contains one or more mutations to facilitate the knob-in-hole interaction. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A or Y407V. In some embodiments, the mutations are:

[0699] (a) T366Y and Y407T in human IgG1 or T366Y / F405A and T394W / Y407T, or

[0700] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0701] T366W / K392C and T366S / L368A / D399C / Y407V;

[0702] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0703] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0704] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0705] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0706] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0707] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0708] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0709] In some embodiments, the present disclosure provides a composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising:

[0710] (a) a first heavy chain selected from:

[0711] (i) SEQ ID NO:79,

[0712] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0713] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0714] (ii) SEQ ID NO:88,

[0715] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0716] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[0717] or

[0718] (iii) SEQ ID NO: 114,

[0719] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0720] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof

[0721] (b) A second heavy chain, said second heavy chain selected from:

[0722] (i.) SEQ ID NO: 117,

[0723] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0724] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[0725] or

[0726] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0727] (ii.) SEQ ID NO: 119,

[0728] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0729] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0730] or

[0731] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0732] (iii.) SEQ ID NO:118,

[0733] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0734] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0735] or

[0736] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0737] (iv.) SEQ ID NO:120,

[0738] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0739] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[0740] or

[0741] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[0742] and

[0743] (c) A light chain, wherein the light chain is selected from:

[0744] (i) SEQ ID NO: 67,

[0745] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0746] A light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0747] (ii) SEQ ID NO: 66

[0748] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0749] A light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0750] or

[0751] (iii) SEQ ID NO: 65,

[0752] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0753] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[0754] wherein:

[0755] any of the above sequences in sub-item (a) optionally may have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[0756] any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[0757] For example, the linker of GGGGS GGGGSGGGGS (SEQ ID NO:50) exemplified in various embodiments herein (above and below) may be replaced by a linker of LE, SEQ ID NO:51, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, or SEQ ID NO:131.

[0758] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0759] In some embodiments, the antibody is formed by a knob-in-hole interaction in the Fc region. In some embodiments, the human IgG Fc contains one or more mutations to facilitate the knob-in-hole interaction. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are:

[0760] (a) T366Y and Y407T, or T366Y / F405A and T394W / Y407T in human IgG1, or

[0761] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0762] T366W / K392C and T366S / L368A / D399C / Y407V;

[0763] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0764] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0765] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0766] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0767] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0768] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0769] In some embodiments, the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutation is the L234A and L235A (LALA) substitution in human IgG1. In some embodiments, the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0770] In some embodiments, a composition is disclosed herein that comprises an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising:

[0771] (a) A first heavy chain selected from:

[0772] (i) SEQ ID NO:79,

[0773] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0774] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[0775] (ii) SEQ ID NO: 88,

[0776] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0777] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[0778] or

[0779] (iii) SEQ ID NO: 114,

[0780] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0781] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof,

[0782] (b) A second heavy chain, the second heavy chain selected from:

[0783] (i) SEQ ID NO: 121,

[0784] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0785] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof,

[0786] (ii) SEQ ID NO: 123,

[0787] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0788] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof,

[0789] (iii) SEQ ID NO: 125,

[0790] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0791] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof,

[0792] (iv) SEQ ID NO: 127,

[0793] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0794] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof,

[0795] (v) SEQ ID NO:129,

[0796] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0797] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof,

[0798] and

[0799] (c) a first light chain selected from:

[0800] (i) SEQ ID NO:67,

[0801] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0802] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0803] (ii) SEQ ID NO:66,

[0804] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0805] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0806] or

[0807] (iii) SEQ ID NO:65,

[0808] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0809] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0810] and

[0811] (d) a second light chain selected from:

[0812] (i) SEQ ID NO:122,

[0813] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0814] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof, or

[0815] (ii) SEQ ID NO:124,

[0816] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0817] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, or

[0818] (iii) SEQ ID NO:126,

[0819] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0820] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof, or

[0821] (iv) SEQ ID NO: 128,

[0822] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0823] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof; or

[0824] (v) SEQ ID NO: 130

[0825] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0826] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof, or

[0827] wherein:

[0828] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO: 46)) added to the N-terminus or C-terminus, and

[0829] Any of the above sequences optionally has a linker comprising one or more glycines and serines, which linker is replaced by another peptide linker or a functionally equivalent variant thereof.

[0830] In some embodiments, a bispecific antibody is disclosed herein, wherein the bispecific antibody comprises three polypeptides (e.g., a first polypeptide, a second polypeptide, and a third polypeptide) that form a first antigen-binding domain that binds CLDN6 and a second antigen-binding domain that binds CD3. In some embodiments, the first polypeptide comprises a first light chain that comprises a first variable light chain region (first V L ), wherein the first variable light chain region comprises a CDR1 sequence having the amino acid sequence of SEQ ID NO:1, a CDR2 sequence having the amino acid sequence of SEQ ID NO:2, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:3. In some embodiments, the second polypeptide comprises a first heavy chain that comprises a first variable heavy chain region (first V H ), wherein the first variable heavy chain region comprises a CDR1 sequence having the amino acid sequence of SEQ ID NO:4, a CDR2 sequence having the amino acid sequence of SEQ ID NO:5, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:6. In some embodiments, the third polypeptide comprises a second heavy chain and a second light chain, wherein the second heavy chain comprises a second variable heavy chain region (second V H ), and the second variable heavy chain region comprises a CDR1 sequence having the amino acid sequence of SEQ ID NO:25, a CDR2 sequence having the amino acid sequence of SEQ ID NO:26, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:27; wherein the second light chain comprises a second variable light chain region (second V L ), and the second variable light chain region comprises a CDR1 sequence having the amino sequence of SEQ ID NO:28, a CDR2 sequence having the amino acid sequence of SEQ ID NO:29, and a CDR3 sequence having the amino acid sequence of SEQ ID NO:30. In some embodiments, the second heavy chain and the second light chain are linked by a peptide linker. In some embodiments, the peptide linker is as described herein. In some embodiments, the peptide linker comprises the amino acid sequence of SEQ ID NO:53. In some embodiments, a peptide linker comprising one or more glycines and serines is replaced by another peptide linker or a functional equivalent variant thereof. In some embodiments, the first V L and the first V H interact to form an antigen-binding domain that binds CLDN6. In some embodiments, the second V L and the second V H interact to form an antigen-binding domain that binds CD3. In some embodiments, the second V L and the second V H are in the scFv format. In some embodiments, the first V L and the first VH is of the Fab type or a fragment thereof.

[0831] In some embodiments, the first variable light chain region of the first polypeptide comprises the amino acid sequence of SEQ ID NO:68, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0832] In some embodiments, the first variable heavy chain region of the second polypeptide comprises the amino acid sequence of SEQ ID NO:69, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0833] In some embodiments, the second variable heavy chain region of the third polypeptide comprises the following amino acid sequence:

[0834] EVQLVESGGGLVQPGGSLRLSCAASGFTFSTYAMNWVRQAPGKGLEWVGRIRSKYNNYATYYADSVKGRFTISRDDSKNTLYLQMNSLRAEDTAVYYCVRHGNFGDSYVSWFAYWGQGTLVTVSS (SEQ ID NO:70),

[0835] or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0836] In some embodiments, the second variable light chain region of the third polypeptide comprises the following amino acid sequence:

[0837] QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTTSNYANWVQQKPGKSPRGLIGGTNKRAPGVPARFSGSLLGGKAALTISGAQPEDEADYYCALWYSNHWVFGGGTKLTVL (SEQ ID NO:71),

[0838] or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0839] In some embodiments, the first polypeptide of the impaired light chain comprises a first variable light chain region and a light chain constant domain that can be referred to as a first light chain constant domain. In some embodiments, the first light chain constant domain comprises the following amino acid sequence:

[0840] GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS(SEQ ID NO:72),

[0841] or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0842] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO:67, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0843] In some embodiments, the second polypeptide that impairs the first heavy chain comprises a first variable heavy chain region and a heavy chain constant domain that can be referred to as the first heavy chain constant domain. In some embodiments, the first heavy chain constant domain comprises the following amino acid sequence:

[0844] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK(SEQ ID NO:73),

[0845] or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0846] In some embodiments, the second polypeptide comprises the amino acid sequence of SEQ ID NO:79, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0847] In some embodiments, the third polypeptide comprises a constant domain. In some embodiments, the constant domain is linked to the C-terminus of the second variable light chain region. In some embodiments, there is no peptide linker between the C-terminus of the second variable light chain region and the constant domain. In some embodiments, the constant domain present in the third polypeptide comprises the following amino acid sequence:

[0848] ASPKSSDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO:74),

[0849] or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0850] In some embodiments, the third polypeptide comprises the amino acid sequence of SEQ ID NO:89, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto.

[0851] In some embodiments, the first polypeptide comprises the amino acid sequence of SEQ ID NO:67; the second polypeptide comprises the amino acid sequence of SEQ ID NO:79; and the third polypeptide comprises the amino acid sequence of SEQ ID NO:89.

[0852] As used herein, the term constant domain refers to the Fc domain. The constant domains exemplified above are optional embodiments, and other constant domains may replace the constant domains described herein.

[0853] In some embodiments, the Fc is from IgG. In some embodiments, the IgG is human IgG. In some embodiments, the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[0854] In some embodiments, the antibody is formed by knob-in-hole interactions in the Fc region. In some embodiments, the human IgG Fc contains one or more mutations to facilitate knob-in-hole interactions. In some embodiments, the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V. In some embodiments, the mutations are:

[0855] (a) T366Y and Y407T in human IgG1 or T366Y / F405A and T394W / Y407T, or

[0856] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[0857] T366W / K392C and T366S / L368A / D399C / Y407V;

[0858] S354C / T366W and Y349C / T366S / L368A / Y407V;

[0859] Y349C / T366W and S354C / T366S / L368A / Y407V;

[0860] E356C / T366W and Y349C / T366S / L368A / Y407V;

[0861] Y349C / T366W and E356C / T366S / L368A / Y407V;

[0862] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[0863] Y349C / T366W and E357C / T366S / L368A / Y407V.

[0864] In some embodiments, the human IgG Fc contains one or more mutations to reduce or eliminate the effector functions of the Fc domain. In some embodiments, the mutations are the L234A and L235A (LALA) substitutions in human IgG1. In some embodiments, the human IgG Fc contains one or more mutations to stabilize the hinge region in the Fc domain. In some embodiments, the mutation is S228P.

[0865] In some embodiments, the composition binds both claudin 6 and CD3 simultaneously.

[0866] In some embodiments, the composition binds to Claudin 6 with an affinity less than 10 nM and at least 100-fold the affinity for Claudin 9, Claudin 3, and / or Claudin 4.

[0867] In any of the embodiments disclosed herein, the composition induces cytotoxicity.

[0868] In any of the embodiments disclosed herein, the composition induces T cell cytotoxicity.

[0869] In any of the embodiments disclosed herein, the composition induces T cell-dependent cytotoxicity.

[0870] In any of the embodiments disclosed herein, the composition increases the expression and / or release of one or more cytokines. In any of the embodiments disclosed herein, the composition increases the expression and / or release of one or more cytokines selected from IL-2, IL-6, IL-10, IFN-γ, and TNF-α.

[0871] As provided herein, the antibody can be formed by heterodimerization of two Fc domains linked to the antibody variable domain, and the antibody variable domain can be VH or an antibody linked to the scFv format. In some embodiments, the antibody polypeptide comprises a first constant domain and a second constant domain. The constant domain can be based on IgG1, IgG2, IgG3, or IgG4. In some embodiments, the constant domain is a human constant domain. As provided herein, the constant domain is based on the human IgG1 constant domain provided herein. These constant domains can be incorporated into any format of the antibody provided herein.

[0872] In some embodiments, the first constant domain comprises a T366W mutation and the second constant domain comprises T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises T366Y and Y407T mutations or T366Y and F405A mutations, and the second constant domain comprises T394W and Y407T mutations. In some embodiments, the first constant domain comprises T366W and D399C mutations, and the second constant domain comprises T366S, L368A, K392C, and Y407V mutations. In some embodiments, the first constant domain comprises T366W and K392C mutations, and the second constant domain comprises T366S, L368A, D399C, and Y407V mutations. In some embodiments, the first constant domain comprises S354C and T366W mutations, and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises Y349C and T366W mutations, and the second constant domain comprises S354C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises E356C and T366W mutations, and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises Y349C and T366W mutations, and the second constant domain comprises E356C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises E357C and T366W mutations, and the second constant domain comprises Y349C, T366S, L368A, and Y407V mutations. In some embodiments, the first constant domain comprises Y349C and T366W mutations, and the second constant domain comprises E357C, T366S, L368A, and Y407V mutations.

[0873] In some embodiments, the first constant domain and the second constant domain each independently comprise L234A and L235A (LALA) substitutions, where the numbering is according to the EU numbering in human IgG1. In some embodiments, the first constant domain and the second constant domain each comprise L234A and L235A (LALA) substitutions.

[0874] Constant domains (Fc) such as the first and second constant domains may also comprise other mutations as provided herein. These mutations may confer increased specificity for Fc receptor types such as FcγRIIA.

[0875] Drug composition

[0876] In some embodiments, a pharmaceutical composition is disclosed herein that comprises the isolated antibody or nucleic acid molecule encoding the antibody as described in any one of the foregoing embodiments. In some embodiments, the composition is an injectable pharmaceutical composition. In some embodiments, the composition is sterile. In some embodiments, the composition is pyrogen-free.

[0877] In addition, this document also provides pharmaceutical compositions that comprise a combination of a composition as described herein with a pharmaceutically acceptable carrier. A “pharmaceutically acceptable carrier” (also referred to as an “excipient” or “carrier”) is a pharmaceutically acceptable solvent, suspending agent, stabilizer, or any other pharmacologically inert vehicle for delivering one or more therapeutic compounds to a subject (e.g., a mammal such as a human, non-human primate, dog, cat, sheep, pig, horse, cow, mouse, rat, or rabbit), which carrier is non-toxic to cells or subjects exposed thereto at the dosages and concentrations employed. A pharmaceutically acceptable carrier can be liquid or solid and can be selected according to the intended mode of administration so as to provide the desired volume, consistency, and other relevant transport and chemical properties when combined with one or more therapeutic compounds and any other components of a given pharmaceutical composition. Exemplary pharmaceutically acceptable carriers that do not react detrimentally with amino acids include, for example but not limited to: water, saline solutions, binders (e.g., polyvinylpyrrolidone or hydroxypropylmethylcellulose); fillers (e.g., lactose and other sugars, gelatin, or calcium sulfate), lubricants (e.g., starch, polyethylene glycol, or sodium acetate), disintegrants (e.g., starch or sodium starch glycolate), and wetting agents (e.g., sodium lauryl sulfate). Pharmaceutically acceptable carriers also include aqueous pH buffer solutions or liposomes (small vesicles composed of various types of lipids, phospholipids, and / or surfactants, which can be used to deliver drugs to mammals). Other examples of pharmaceutically acceptable carriers include buffers such as phosphates, citrates, and other organic acids; antioxidants such as ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrin; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN TM polyethylene glycol (PEG), and PLURONICS TM .

[0878] A pharmaceutical composition can be formulated by mixing one or more active agents with one or more physiologically acceptable carriers, diluents, and / or adjuvants and optionally other agents commonly incorporated into formulations to provide improved transfer, delivery, tolerance, etc. The pharmaceutical composition can be formulated, for example, as a lyophilized formulation, an aqueous solution, a dispersion, or a solid formulation such as a tablet, a dragee, or a capsule. A large number of suitable formulations can be found in all formularies known to pharmaceutical chemists: Remington's Pharmaceutical Sciences (18th Edition, Mack Publishing Company, Easton, PA (1990)), especially Chapter 87 by Block, Lawrence therein. These formulations include, for example, powders, pastes, ointments, gels, waxes, oils, lipids, vesicles containing lipids (cationic or anionic) (e.g., LIPOFECTIN tm ), DNA conjugates, anhydrous absorbent pastes, water-in-oil and oil-in-water emulsions, emulsion polyethylene glycol (polyethylene glycol of various molecular weights), semi-solid gels, and semi-solid mixtures containing polyethylene glycol. Any of the foregoing mixtures may be suitable for the treatments and therapies described herein, provided that the active agent in the formulation is not inactivated by the formulation and the formulation is physiologically compatible with and tolerable to the route of administration. See also Baldrick, Regul Toxicol Pharmacol 32:210-218, 2000; Wang, Int J Pharm 203:1-60, 2000; Charman J Pharm Sci 89:967-978, 2000; and Powell et al., PDA J Pharm Sci Technol 52:238-311, 1998, and additional information related to formulations, excipients, and carriers known to pharmaceutical chemists cited therein.

[0879] Pharmaceutical compositions include, but are not limited to, solutions, emulsions, aqueous suspensions, and liposome-containing formulations. These compositions can be produced from a variety of components, including, for example, preformed liquids, self-emulsifying solids, and self-emulsifying semi-solids. An emulsion is generally a two-phase system composed of two immiscible liquid phases that are intimately mixed and dispersed with each other; generally, emulsions are of the water-in-oil (W / O) or oil-in-water (O / W) type. Emulsion formulations are widely used for oral therapeutic agents because of their ease of formulation and the efficacy of solubilization, absorption, and bioavailability.

[0880] Compositions and formulations can contain a sterile aqueous solution and can also contain buffers, diluents, and other suitable additives (e.g., penetration enhancers, carrier compounds, and other pharmaceutically acceptable carriers). The composition can also contain other auxiliary components conventionally present in pharmaceutical compositions. Thus, the composition can also contain compatible pharmaceutically active materials, such as antipruritics, astringents, local anesthetics, or anti-inflammatory agents, or other materials that can be used to physically formulate the various dosage forms of the compositions provided herein, such as dyes, flavoring agents, preservatives, antioxidants, opacifying agents, thickening agents, and stabilizers. In addition, the composition can be mixed with adjuvants, such as lubricants, preservatives, stabilizers, wetting agents, emulsifying agents, salts for affecting osmotic pressure, buffers, coloring agents, flavoring agents, and fragrances. However, when added, such materials should not unduly interfere with the biological activity of the polypeptide components within the compositions provided herein. When necessary, the formulation can be sterilized.

[0881] In some embodiments, a composition containing the composition provided herein can be in the form of a solution or a powder, with or without a diluent to prepare an injectable suspension. The composition can contain additional components, including but not limited to pharmaceutically acceptable vehicles, such as saline, water, lactose, mannitol, or combinations thereof.

[0882] Any suitable method can be used to administer the composition described herein to a mammal. For example, the administration can be parenteral (e.g., by subcutaneous, intrathecal, intracardiac, intramuscular, or intraperitoneal injection, or by intravenous infusion). The administration can be rapid (e.g., by injection) or can be carried out over a period of time (e.g., by slow infusion or administration of a sustained-release formulation). In some embodiments, the administration can be topical (e.g., transdermal, sublingual, ocular, or intranasal), pulmonary (e.g., by inhalation or insufflation of a powder or aerosol), or oral. Additionally, a composition containing the composition described herein can be administered before, after, or in place of surgical resection of a tumor.

[0883] The antibodies, compositions, or pharmaceutical compositions provided herein can be administered at any suitable interval to achieve the desired effect in a subject. In some embodiments, the antibodies, compositions, or pharmaceutical compositions are administered daily, every other day, weekly, biweekly, triweekly, or monthly (i.e., once every four weeks). In some embodiments, the methods provided herein include administering the cells or the antibodies, compositions, or pharmaceutical compositions to a subject in need thereof at intervals of daily, every other day, weekly, biweekly, triweekly, or monthly (i.e., once every four weeks).

[0884] In some embodiments, a nucleic acid molecule is disclosed herein that encodes the antibody or amino acid sequence described in any of the foregoing embodiments.

[0885] In some embodiments, a vector is disclosed herein that comprises the nucleic acid molecule of any one of the foregoing embodiments.

[0886] In some embodiments, a cell is disclosed herein that comprises the nucleic acid molecule of any one of the foregoing embodiments or the vector of any one of the foregoing embodiments.

[0887] In some embodiments, a method for modulating and / or targeting claudin 6 and CD3 in a biological cell is disclosed herein, the method comprising contacting the cell with the composition of any one of the foregoing embodiments.

[0888] In some embodiments, a method for modulating the activity of claudin 6 in a biological cell is disclosed herein, the method comprising contacting a cell expressing claudin 6 with the composition of any one of the foregoing embodiments.

[0889] In some embodiments, a method for inhibiting the function of claudin 6 in a biological cell is disclosed herein, the method comprising contacting a cell expressing claudin 6 with the composition of any one of the foregoing embodiments.

[0890] Therapeutic method

[0891] In some embodiments, a method for treating or preventing cancer is disclosed herein, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of the foregoing embodiments.

[0892] In some embodiments, the use of the composition of any one of the foregoing embodiments in the preparation of a medicament for treating or preventing cancer is disclosed herein.

[0893] In some embodiments, the methods or uses described in any of the foregoing embodiments are disclosed herein, wherein the cancer is selected from one or more of the following: basal cell carcinoma; biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancers; breast cancer; peritoneal cancer; cervical cancer; choriocarcinoma; colon and rectal cancer; connective tissue cancer; digestive system cancers; endometrial cancer; esophageal cancer; eye cancer; head and neck cancer; gastric cancer (including gastrointestinal cancer); glioblastoma; glioma; liver cancer; hepatoma; intraepithelial neoplasia; kidney cancer or renal carcinoma; laryngeal cancer; leukemia; liver cancer; lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma); melanoma; myeloma; neuroblastoma; oral cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; malignant rhabdoid tumor; rectal cancer; respiratory system cancers; salivary gland cancer; sarcoma; skin cancer; squamous cell carcinoma; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; urinary system cancers; vulvar cancer; lymphoma, including Hodgkin's and non-Hodgkin's lymphoma, and B-cell lymphoma (including low-grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate / follicular NHL; intermediate diffuse NHL; high-grade immunoblastic NHL; high-grade lymphoblastic NHL; high-grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenström's macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphocytic leukemia (ALL); hairy cell leukemia; chronic myelogenous leukemia; and other carcinomas and sarcomas; and post-transplant lymphoproliferative disorder (PTLD), and abnormal vascular proliferation associated with nevus flammeus, edema (e.g., edema associated with brain tumors), and Meigs' syndrome.

[0894] As a non-limiting example, the onset prevention, presence, and / or progression evaluation of cancer in a subject can be assessed according to the Tumor / Nodes / Metastases (TNM) classification system (International Union Against Cancer, 6th edition, 2002) or the Whitmore-Jewett staging system (American Urological Association). Generally, cancer is staged using a combination of physical examination, blood tests, and medical imaging. If tumor tissue is obtained by biopsy or surgery, microscopic examination of the tissue can also provide pathologic staging. In some embodiments, the staging or grading of cancer helps the physician determine the prognosis of the cancer and select an appropriate regulatory therapy.

[0895] In some embodiments, overall staging groups are used as non-limiting examples to evaluate the prevention of the onset or progression of cancer: Stage I cancer is confined to one part of the body, usually in a small area; Stage II cancer is locally advanced and has grown into nearby tissues or lymph nodes, as is Stage III cancer. Whether a cancer is designated as Stage II or III depends on the specific type of cancer. The specific criteria for Stages II and III may vary according to the diagnosis. Stage IV cancer has usually metastasized or spread to other organs or throughout the body. Conventional methods available to those of ordinary skill in the art, such as physical examination, blood tests, and imaging scans (e.g., X-rays, MRI, CT scans, ultrasound, etc.), can be used to evaluate the onset or progression of cancer.

[0896] As disclosed herein, administering or applying a treatment / therapy means a treatment / therapy from which a subject derives a beneficial effect, such as a reduction, decrease, attenuation, weakening, stabilization, remission, containment, inhibition, or suppression of the development or progression of cancer or its symptoms.

[0897] In some embodiments, the treatment / therapy received by the subject or the prevention of the onset of cancer results in at least one or more of the following effects: (1) reducing or improving the severity of cancer and / or genetic disease or disorder and / or symptoms associated therewith; (2) shortening the duration of symptoms associated with cancer and / or genetic disease or disorder; (3) preventing the recurrence of symptoms associated with cancer and / or genetic disease or disorder; (4) causing cancer and / or genetic disease or disorder and / or symptoms associated therewith to regress; (5) reducing the subject's hospitalization; (6) shortening the length of hospitalization; (7) prolonging the subject's survival; (8) inhibiting the progression of cancer and / or genetic disease or disorder and / or symptoms associated therewith; (9) enhancing or improving the therapeutic effect of another therapy; (10) reducing or eliminating cell populations associated with cancer and / or genetic disease or disorder; (11) reducing the growth of tumors or neoplasms; (12) reducing tumor size; (13) reducing tumor formation; (14) eradicating, removing, or controlling primary, regional, and / or metastatic cancer; (15) reducing the number or size of metastases; (16) reducing mortality; (17) increasing the cancer-free survival rate of the subject; (18) prolonging the recurrence-free survival; (19) increasing the number of subjects in remission; (20) reducing the hospitalization rate; (21) as measured by conventional methods available to those skilled in the art (e.g., X-ray, MRI, CAT scan, ultrasound, etc.), after administration of the therapy, the size of the tumor is maintained and does not increase or the size of the tumor increases by less than 5% or 10%; (22) preventing the development or onset of cancer and / or genetic disease or disorder and / or symptoms associated therewith; (23) increasing the duration of remission of the subject; (24) reducing the number of symptoms associated with cancer and / or genetic disease or disorder; (25) prolonging the asymptomatic survival of cancer subjects and / or subjects associated with genetic disease or disorder; and / or (26) restricting or reducing metastasis. In some embodiments, the treatment / therapy received by the subject does not cure cancer but arrests the progression or worsening of the disease. In certain embodiments, the treatment / therapy received by the subject does not prevent the onset / development of cancer but may prevent the onset of cancer symptoms.

[0898] In some embodiments, the treated subject does not develop cytokine release syndrome (CRS), or does not develop significant CRS-related clinical symptoms or toxicities. These symptoms include, but are not limited to, fever, chills, fatigue, weakness, anorexia, nausea, vomiting, diarrhea, headache, joint or muscle pain, rash, hypotension, increased heart rate, arrhythmia, tachycardia, decreased cardiac function, swelling, fluid accumulation (edema), confusion, dizziness, seizure, hallucination, decreased coordination, problems with speaking or swallowing, tremors, problems controlling movement, cough, shortness of breath, tachypnea, decreased lung function, decreased oxygen levels, decreased renal or liver function, increased cytokine levels in the blood, electrolyte changes, and coagulation changes. In some embodiments, after administration of an antibody as provided herein, the blood levels of interleukin-6 (IL-6), interleukin-10 (IL-10), interferon (IFN)-γ, monocyte chemoattractant protein 1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF), IL-1, IL-2, IL-2-receptor-α, or IL-8 do not increase or do not increase significantly.

[0899] In some embodiments, "preventing" the onset or progression of cancer in a subject in need thereof is inhibiting or blocking the cancer or disorder. In some embodiments, the methods disclosed herein prevent or inhibit the cancer or disorder at any amount or level. In some embodiments, the methods disclosed herein prevent or inhibit the cancer or genetic disease or disorder with at least or about 10% inhibition (e.g., at least or about 20% inhibition, at least or about 30% inhibition, at least or about 40% inhibition, at least or about 50% inhibition, at least or about 60% inhibition, at least or about 70% inhibition, at least or about 80% inhibition, at least or about 90% inhibition, at least or about 95% inhibition, at least or about 98% inhibition, or at least or about 100% inhibition).

[0900] In some embodiments, there is provided an isolated antibody that comprises one or more of the sequences disclosed herein.

[0901] As used herein, the term "comprising" and variations thereof are intended to be non-limiting, such that the listing of items in a list does not exclude other similar items that may also be used in the materials, compositions, devices, and methods of the present technology. Similarly, the terms "can" and "may" and variations thereof are intended to be non-limiting, such that the recitation that an embodiment can or may include certain elements or features does not exclude other embodiments of the inventive technology that do not contain those elements or features. Although the open-ended term "comprising", which is a synonym for terms such as including, containing, or having, is used herein to describe and claim the present disclosure, the technology of the present invention or its embodiments may alternatively be described using more restrictive terms such as "consisting of the listed ingredients" or "consisting essentially of the listed ingredients".

[0902] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are described herein. All publications, patents, and patent publications cited herein are hereby incorporated by reference in their entirety for all purposes.

[0903] Enumerated embodiments

[0904] In some embodiments, the following embodiments are provided:

[0905] 1. A composition comprising a tandem single-chain variable fragment (scFv) specific for claudin 6 and CD3, the tandem single-chain variable fragment (scFv) comprising one or more of the following:

[0906] I.

[0907] (a) The amino acid sequence of SEQ ID NO:82, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0908] (b)

[0909] (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0910] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0911] (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:8 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0912] (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:10 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:11 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:12 or a variant thereof,

[0913] II.

[0914] (a) the amino acid sequence of SEQ ID NO.83, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0915] (b)

[0916] (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0917] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0918] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:8 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0919] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:10 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:11 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:12 or a variant thereof,

[0920] III.

[0921] (a) The amino acid sequence of SEQ ID NO.84, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0922] (b)

[0923] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0924] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, and

[0925] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0926] IV.

[0927] (a) The amino acid sequence of SEQ ID NO:85, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0928] (b)

[0929] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0930] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, and

[0931] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[0932] V.

[0933] (a) The amino acid sequence of SEQ ID NO.93, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0934] (b)

[0935] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0936] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0937] (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, and

[0938] (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof,

[0939] VI.

[0940] (a) the amino acid sequence of SEQ ID NO.94, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0941] (b)

[0942] (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0943] (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0944] (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, and

[0945] (iv) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof,

[0946] VII.

[0947] (a) The amino acid sequence of SEQ ID NO.95, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0948] (b)

[0949] (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0950] (ii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0951] (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, and

[0952] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof,

[0953] VIII.

[0954] (a) The amino acid sequence of SEQ ID NO.96, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0955] (b)

[0956] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0957] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0958] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, and

[0959] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof,

[0960] IX.

[0961] (a) The amino acid sequence of SEQ ID NO.97, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0962] (b)

[0963] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0964] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0965] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, and

[0966] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof,

[0967] X.

[0968] (a) The amino acid sequence of SEQ ID NO.98, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0969] (b)

[0970] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0971] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0972] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, and

[0973] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof,

[0974] XI.

[0975] (a) The amino acid sequence of SEQ ID NO.99, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0976] (b)

[0977] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0978] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0979] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0980] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof,

[0981] XII.

[0982] (a) The amino acid sequence of SEQ ID NO.100, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0983] (b)

[0984] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0985] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[0986] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and

[0987] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof,

[0988] XIII.

[0989] (a) The amino acid sequence of SEQ ID NO:109, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0990] (b)

[0991] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[0992] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[0993] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, and

[0994] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof, and

[0995] XIV.

[0996] (a) The amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[0997] (b)

[0998] (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[0999] (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[1000] (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof, and

[1001] (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof, or

[1002] Wherein:

[1003] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[1004] Any of the above sequences optionally has a linker containing one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[1005] 2. A composition comprising an scFv-FabFc antibody specific for claudin 6 and CD3, the antibody comprising:

[1006] (a) A first heavy chain selected from:

[1007] (i) SEQ ID NO:79,

[1008] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1009] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[1010] (ii) SEQ ID NO:88,

[1011] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1012] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[1013] Or

[1014] (iii) SEQ ID NO:114,

[1015] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1016] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof,

[1017] (b) A second heavy chain selected from:

[1018] (i.) SEQ ID NO: 80,

[1019] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1020] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof, or

[1021] (ii.) SEQ ID NO: 89,

[1022] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1023] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, or

[1024] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, or

[1025] (iii.) SEQ ID NO: 90,

[1026] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1027] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, or

[1028] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:48 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, or

[1029] (iv.) SEQ ID NO:91,

[1030] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1031] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, or

[1032] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:49 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof, or

[1033] (v.) SEQ ID NO:92,

[1034] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1035] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, or

[1036] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, or

[1037] (vi.) SEQ ID NO:111,

[1038] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1039] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, or

[1040] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof,

[1041] and

[1042] (c) A first light chain, wherein the first light chain is selected from:

[1043] (i) SEQ ID NO:67,

[1044] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1045] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[1046] (ii) SEQ ID NO:66,

[1047] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1048] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[1049] or

[1050] (iii) SEQ ID NO:65,

[1051] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1052] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[1053] wherein:

[1054] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[1055] Any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[1056] 3. The composition according to embodiment 2, wherein the Fc is from IgG.

[1057] 4. The composition according to embodiment 3, wherein the IgG is human IgG.

[1058] 5. The composition according to embodiment 4, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[1059] 6. The composition according to any one of embodiments 2 to 5, wherein the antibody is formed by a knobs-into-holes interaction in the Fc region.

[1060] 7. The composition according to embodiment 4 or embodiment 5, wherein the human IgG Fc comprises one or more mutations to facilitate knobs-into-holes interaction.

[1061] 8. The composition according to embodiment 7, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V.

[1062] 9. The composition according to embodiment 7, wherein the mutation is selected from:

[1063] (a) T366Y and Y407T in human IgG1, or T366Y / F405A and T394W / Y407T, or

[1064] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[1065] T366W / K392C and T366S / L368A / D399C / Y407V;

[1066] S354C / T366W and Y349C / T366S / L368A / Y407V;

[1067] Y349C / T366W and S354C / T366S / L368A / Y407V;

[1068] E356C / T366W and Y349C / T366S / L368A / Y407V;

[1069] Y349C / T366W and E356C / T366S / L368A / Y407V;

[1070] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[1071] Y349C / T366W and E357C / T366S / L368A / Y407V.

[1072] 10. The composition according to embodiment 4, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain.

[1073] 11. The composition according to embodiment 10, wherein the mutation is the L234A and L235A (LALA) substitution in human IgG1.

[1074] 12. The composition according to embodiment 4, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[1075] 13. The composition according to embodiment 12, wherein the mutation is S228P.

[1076] 14. A composition comprising an IgG-(scFV)2 antibody specific for claudin 6 and CD3, the antibody comprising:

[1077] (a) a heavy chain selected from:

[1078] (i.) SEQ ID NO:86,

[1079] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1080] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[1081] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof,

[1082] (ii.) SEQ ID NO:87,

[1083] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1084] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[1085] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[1086] (iii.) SEQ ID NO: 101,

[1087] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1088] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[1089] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof, or

[1090] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof,

[1091] (iv.) SEQ ID NO: 102,

[1092] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1093] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[1094] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof, or

[1095] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof,

[1096] (v.) SEQ ID NO: 103,

[1097] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1098] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[1099] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, or

[1100] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof,

[1101] (vi.) SEQ ID NO: 104,

[1102] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1103] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[1104] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, or

[1105] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof,

[1106] (vii.) SEQ ID NO: 105,

[1107] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1108] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[1109] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof, or

[1110] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof,

[1111] (viii.) SEQ ID NO: 106,

[1112] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1113] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[1114] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof, or

[1115] A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof,

[1116] (ix.) SEQ ID NO: 107,

[1117] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1118] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or

[1119] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, or

[1120] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof,

[1121] (x.) SEQ ID NO:108,

[1122] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1123] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or

[1124] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, or

[1125] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof,

[1126] (xi.) SEQ ID NO: 112,

[1127] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1128] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, or

[1129] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof, or

[1130] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof,

[1131] (xii.) SEQ ID NO: 113,

[1132] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1133] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, or

[1134] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof, or

[1135] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof,

[1136] and

[1137] (b) A light chain selected from:

[1138] (i) SEQ ID NO: 67,

[1139] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1140] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[1141] (ii) SEQ ID NO: 66,

[1142] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1143] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[1144] or

[1145] (iii) SEQ ID NO: 65,

[1146] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1147] a light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[1148] wherein:

[1149] any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[1150] any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[1151] 15. The composition according to embodiment 14, wherein the Fc is from IgG.

[1152] 16. The composition according to embodiment 15, wherein the IgG is human IgG.

[1153] 17. The composition according to embodiment 16, wherein the human IgG is selected from IgG1, IgG2, IgG3 and IgG4.

[1154] 18. The composition according to embodiment 16, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain.

[1155] 19. The composition according to embodiment 18, wherein the mutation is the L234A and L235A (LALA) substitution in human IgG1.

[1156] 20. The composition according to embodiment 16, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[1157] 21. The composition according to embodiment 20, wherein the mutation is S228P.

[1158] 22. A composition, the composition comprising a scFv-FabFc antibody specific for claudin 6 and CD3, the antibody comprising:

[1159] (a) A first heavy chain selected from:

[1160] (i) SEQ ID NO:79,

[1161] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1162] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[1163] (ii) SEQ ID NO:88,

[1164] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1165] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[1166] Or

[1167] (iii) SEQ ID NO:114,

[1168] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1169] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof,

[1170] (b) A second heavy chain selected from:

[1171] SEQ ID NO:81,

[1172] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1173] a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[1174] and

[1175] (c) a light chain selected from:

[1176] (i) SEQ ID NO: 67,

[1177] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1178] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[1179] (ii) SEQ ID NO: 66

[1180] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1181] a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof,

[1182] or

[1183] (iii) SEQ ID NO: 65,

[1184] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1185] A light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of ID NO:1 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[1186] wherein:

[1187] Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[1188] Any of the above sequences optionally has a linker comprising one or more glycines and serines, and said linker is replaced by another peptide linker or a functional equivalent variant thereof.

[1189] 23. The composition according to embodiment 22, wherein the Fc is from IgG.

[1190] 24. The composition according to embodiment 23, wherein the IgG is human IgG.

[1191] 25. The composition according to embodiment 24, wherein the human IgG is selected from IgG1, IgG2, IgG3 and IgG4.

[1192] 26. The composition according to any one of embodiments 22 to 25, wherein the antibody is formed by a knobs-into-holes interaction in the Fc region.

[1193] 27. The composition according to embodiment 24, wherein the human IgG Fc comprises one or more mutations to facilitate knobs-into-holes interaction.

[1194] 28. The composition according to embodiment 27, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A or Y407V.

[1195] 29. The composition according to embodiment 24, wherein the mutation is:

[1196] (a) T366Y and Y407T in human IgG1 or T366Y / F405A and T394W / Y407T, or

[1197] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[1198] T366W / K392C and T366S / L368A / D399C / Y407V;

[1199] S354C / T366W and Y349C / T366S / L368A / Y407V;

[1200] Y349C / T366W and S354C / T366S / L368A / Y407V;

[1201] E356C / T366W and Y349C / T366S / L368A / Y407V;

[1202] Y349C / T366W and E356C / T366S / L368A / Y407V;

[1203] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[1204] Y349C / T366W and E357C / T366S / L368A / Y407V.

[1205] 30. The composition according to embodiment 24, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain.

[1206] 31. The composition according to embodiment 30, wherein the mutation is the L234A and L235A (LALA) substitution in human IgG1.

[1207] 32. The composition according to embodiment 24, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[1208] 33. The composition according to embodiment 32, wherein the mutation is S228P.

[1209] 34. A composition comprising an scFv-FabFc antibody specific for claudin 6 and CD3, the antibody comprising:

[1210] (a) A first heavy chain selected from:

[1211] (i) SEQ ID NO:79,

[1212] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1213] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[1214] (ii) SEQ ID NO: 88,

[1215] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1216] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[1217] Or

[1218] (iii) SEQ ID NO: 114,

[1219] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1220] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof,

[1221] (b) A second heavy chain, the second heavy chain selected from:

[1222] (i.) SEQ ID NO: 117,

[1223] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1224] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[1225] or

[1226] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[1227] (ii.) SEQ ID NO: 119,

[1228] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1229] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[1230] or

[1231] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[1232] (iii.) SEQ ID NO: 118,

[1233] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1234] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[1235] or

[1236] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof,

[1237] (iv.) SEQ ID NO: 120,

[1238] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1239] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 18 or a variant thereof,

[1240] or

[1241] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof,

[1242] and

[1243] (c) a light chain, wherein the light chain is selected from:

[1244] (i) SEQ ID NO: 67,

[1245] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1246] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[1247] (ii) SEQ ID NO:66,

[1248] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1249] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[1250] or

[1251] (iii) SEQ ID NO:65,

[1252] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1253] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or

[1254] wherein:

[1255] any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[1256] any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

[1257] 35. The composition according to embodiment 34, wherein the Fc is from IgG.

[1258] 36. The composition according to embodiment 35, wherein the IgG is human IgG.

[1259] 37. The composition according to embodiment 36, wherein the human IgG is selected from IgG1, IgG2, IgG3, and IgG4.

[1260] 38. The composition according to any one of embodiments 34 to 37, wherein the antibody is formed by a knob-into-hole interaction in the Fc region.

[1261] 39. The composition according to embodiment 36, wherein the human IgG Fc comprises one or more mutations to facilitate the knob-into-hole interaction.

[1262] 40. The composition according to embodiment 39, wherein the mutation is selected from (i) T366Y or T366W, and (ii) Y407T, Y407A, or Y407V.

[1263] 41. The composition according to embodiment 36, wherein the mutation is:

[1264] (a) T366Y and Y407T or T366Y / F405A and T394W / Y407T in human IgG1, or

[1265] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[1266] T366W / K392C and T366S / L368A / D399C / Y407V;

[1267] S354C / T366W and Y349C / T366S / L368A / Y407V;

[1268] Y349C / T366W and S354C / T366S / L368A / Y407V;

[1269] E356C / T366W and Y349C / T366S / L368A / Y407V;

[1270] Y349C / T366W and E356C / T366S / L368A / Y407V;

[1271] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[1272] Y349C / T366W and E357C / T366S / L368A / Y407V.

[1273] 42. The composition according to embodiment 36, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate the effector functions of the Fc domain.

[1274] 43. The composition according to embodiment 42, wherein the mutations are the L234A and L235A (LALA) substitutions in human IgG1.

[1275] 44. The composition according to embodiment 36, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[1276] 45. The composition according to embodiment 44, wherein the mutation is S228P.

[1277] 46. A composition comprising a scFv-FabFc antibody specific for claudin 6 and CD3, the antibody comprising:

[1278] (a) A first heavy chain selected from:

[1279] (i) SEQ ID NO:79,

[1280] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1281] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof,

[1282] (ii) SEQ ID NO:88,

[1283] An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1284] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof,

[1285] Or

[1286] (iii) SEQ ID NO: 114,

[1287] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1288] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 47 or a variant thereof,

[1289] (b) A second heavy chain, said second heavy chain selected from:

[1290] (i) SEQ ID NO: 121,

[1291] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1292] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof,

[1293] (ii) SEQ ID NO: 123,

[1294] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1295] a heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 31 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 32 or a variant thereof,

[1296] (iii) SEQ ID NO: 125,

[1297] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1298] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof,

[1299] (iv) SEQ ID NO: 127,

[1300] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1301] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof,

[1302] (v) SEQ ID NO: 129,

[1303] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1304] A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof,

[1305] and

[1306] (c) A first light chain, the first light chain selected from:

[1307] (i) SEQ ID NO: 67,

[1308] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1309] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[1310] (ii) SEQ ID NO:66,

[1311] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1312] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ IDNO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof,

[1313] or

[1314] (iii) SEQ ID NO:65,

[1315] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1316] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ IDNO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof

[1317] and

[1318] (d) A second light chain, the second light chain selected from:

[1319] (i) SEQ ID NO:122,

[1320] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1321] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, or

[1322] (ii) SEQ ID NO: 124,

[1323] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1324] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 33 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 34 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 35 or a variant thereof, or

[1325] (iii) SEQ ID NO: 126,

[1326] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1327] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof, or

[1328] (iv) SEQ ID NO: 128,

[1329] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1330] A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO: 37 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO: 38 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO: 39 or a variant thereof, or

[1331] (v) SEQ ID NO:130,

[1332] an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or

[1333] a light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, or

[1334] wherein:

[1335] any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and

[1336] any of the above sequences optionally has a linker comprising one or more glycines and serines, and said linker is replaced by another peptide linker or a functional equivalent variant thereof.

[1337] 47. The composition according to embodiment 46, wherein the Fc is from IgG.

[1338] 48. The composition according to embodiment 47, wherein the IgG is human IgG.

[1339] 49. The composition according to embodiment 48, wherein the human IgG is selected from IgG1, IgG2, IgG3 and IgG4.

[1340] 50. The composition according to any one of embodiments 46 to 49, wherein the antibody is formed by a knob-in-hole interaction in the Fc region.

[1341] 51. The composition according to embodiment 46, wherein the human IgG Fc comprises one or more mutations to facilitate knob-in-hole interaction.

[1342] 52. The composition according to embodiment 51, wherein the mutations are selected from (i) T366Y or T366W, and (ii) Y407T, Y407A or Y407V.

[1343] 53. The composition according to embodiment 51, wherein the mutations are:

[1344] (a) T366Y and Y407T in human IgG1, or T366Y / F405A and T394W / Y407T, or

[1345] (b) T366W / D399C and T366S / L368A / K392C / Y407V in human IgG1;

[1346] T366W / K392C and T366S / L368A / D399C / Y407V;

[1347] S354C / T366W and Y349C / T366S / L368A / Y407V;

[1348] Y349C / T366W and S354C / T366S / L368A / Y407V;

[1349] E356C / T366W and Y349C / T366S / L368A / Y407V;

[1350] Y349C / T366W and E356C / T366S / L368A / Y407V;

[1351] E357C / T366W and Y349C / T366S / L368A / Y407V; or

[1352] Y349C / T366W and E357C / T366S / L368A / Y407V.

[1353] 54. The composition according to embodiment 46, wherein the human IgG Fc comprises one or more mutations to reduce or eliminate the effector function of the Fc domain.

[1354] 55. The composition according to embodiment 54, wherein the mutation is the L234A and L235A (LALA) substitution in human IgG1.

[1355] 56. The composition according to embodiment 46, wherein the human IgG Fc comprises one or more mutations to stabilize the hinge region in the Fc domain.

[1356] 57. The composition according to embodiment 56, wherein the mutation is S228P.

[1357] 58. The composition according to any one of embodiments 1 to 57, wherein the composition binds both claudin-6 and CD3 simultaneously.

[1358] 59. The composition according to any one of embodiments 1 to 58, wherein the composition binds claudin-6 with an affinity of less than 10 nM and with an affinity that is at least 100-fold that for claudin-9, claudin-3, and / or claudin-4.

[1359] 60. A pharmaceutical composition, the pharmaceutical composition comprising the isolated antibody or nucleic acid molecule encoding the antibody as described in any one of embodiments 1 to 59.

[1360] 61. The pharmaceutical composition as described in embodiment 60, wherein the composition is an injectable pharmaceutical composition.

[1361] 62. The pharmaceutical composition as described in embodiment 60 or 61, wherein the composition is sterile.

[1362] 63. The pharmaceutical composition as described in any one of embodiments 60 to 62, wherein the composition is pyrogen-free.

[1363] 64. A nucleic acid molecule, the nucleic acid molecule encoding the antibody or amino acid sequence as described in any one of the foregoing embodiments.

[1364] 65. A vector, the vector comprising the nucleic acid molecule as described in embodiment 64.

[1365] 66. A cell, the cell comprising the nucleic acid molecule as described in embodiment 64 or the vector as described in embodiment 65.

[1366] 67. A method for modulating and / or targeting Claudin 6 and CD3 in biological cells, the method comprising contacting the cells with the composition as described in any one of embodiments 1 to 59.

[1367] 68. A method for modulating the activity of Claudin 6 in biological cells, the method comprising contacting cells expressing Claudin 6 with the composition as described in any one of embodiments 1 to 59.

[1368] 69. A method for inhibiting the function of Claudin 6 in biological cells, the method comprising contacting cells expressing Claudin 6 with the composition as described in any one of embodiments 1 to 59.

[1369] 70. A method for treating or preventing cancer, the method comprising administering to a subject in need thereof an effective amount of the composition as described in any one of embodiments 1 to 59.

[1370] 71. Use of the composition as described in any one of embodiments 1 to 59 in the preparation of a medicament for treating and preventing cancer.

[1371] 72. The method or use according to any one of embodiments 1 to 71, wherein the cancer is selected from one or more of the following: basal cell carcinoma; biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; peritoneal cancer; cervical cancer; choriocarcinoma; colon and rectal cancer; connective tissue cancer; digestive system cancer; endometrial cancer; esophageal cancer; eye cancer; head and neck cancer; gastric cancer (including gastrointestinal cancer); glioblastoma; glioma; liver cancer; hepatoma; intraepithelial neoplasia; kidney cancer or renal carcinoma; laryngeal cancer; leukemia; liver cancer; lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma); melanoma; myeloma; neuroblastoma; oral cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancre...

Claims

1. A bispecific antibody that binds CLDN6 and CD3, the bispecific antibody comprising: A first polypeptide, the first polypeptide comprising a first light chain containing a first variable light chain region, wherein the first variable light chain region comprises: (1) A CDR1 sequence that comprises the amino acid sequence of SEQ ID NO:1; (2) A CDR2 sequence that comprises the amino acid sequence of SEQ ID NO:2; and (3) A CDR3 sequence that comprises the amino acid sequence of SEQ ID NO:3; A second polypeptide, the second polypeptide comprising a first heavy chain containing a first variable heavy chain region, wherein the first variable heavy chain region comprises: (1) CDR1, which comprises the amino acid sequence of SEQ ID NO:4; (2) CDR2, which comprises the amino acid sequence of SEQ ID NO:5, and (3) CDR3, which comprises the amino acid sequence of SEQ ID NO:6; and A third polypeptide, the third polypeptide comprising a second light chain and a second heavy chain, wherein: The second heavy chain comprises a second variable heavy chain region, the second variable heavy chain region comprising: (1) CDR1, which comprises the amino acid sequence of SEQ ID NO:25; (2) CDR2, which comprises the amino acid sequence of SEQ ID NO:26; and (3) CDR3, which comprises the amino acid sequence of SEQ ID NO:27; and The second light chain comprises a second variable light chain region, the second variable light chain region comprising: (1) CDR1, which comprises the amino sequence of SEQ ID NO:28; (2) CDR2, which comprises the amino acid sequence of SEQ ID NO:29; and (3) CDR3, which comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof.

2. The bispecific antibody according to claim 1, wherein the first variable light chain region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

68.

3. The bispecific antibody according to claim 1, wherein the first variable light chain region comprises the amino acid sequence of SEQ ID NO:

68.

4. The bispecific antibody according to claim 1, wherein the first variable heavy chain region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

69.

5. The bispecific antibody according to claim 4, wherein the first variable heavy chain region comprises the amino acid sequence of SEQ ID NO:

69.

6. The bispecific antibody according to claim 1, wherein the second variable heavy chain region comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

70.

7. The bispecific antibody according to claim 1, wherein the second variable heavy chain region comprises the amino acid sequence of SEQ ID NO:

70.

8. The bispecific antibody according to claim 1, wherein the second variable heavy chain region and the second variable light chain region are linked by a peptide linker.

9. The bispecific antibody according to claim 8, wherein the linker comprises the amino acid sequence of SEQ ID NO:

53.

10. The bispecific antibody according to claim 1, wherein the third polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

89.

11. The bispecific antibody according to claim 1, wherein the third polypeptide has the amino acid sequence of SEQ ID NO:

89.

12. The bispecific antibody according to claim 1, wherein the first polypeptide further comprises a first constant domain, and the third polypeptide further comprises a second constant domain.

13. The bispecific antibody according to claim 12, wherein the first constant domain and the second domain interact with each other to form a heterodimer.

14. The bispecific antibody according to claim 12, wherein the first constant domain and the second constant domain each independently comprise a human IgG Fc domain containing one or more mutations.

15. The bispecific antibody according to claim 14, wherein: i. the first constant domain comprises the T366W mutation, and the second constant domain comprises the T366S, L368A, and Y407V mutations; ii. the first constant domain comprises the T366Y and Y407T mutations or the T366Y and F405A mutations, and the second constant domain comprises the T394W and Y407T mutations; iii. the first constant domain comprises the T366W and D399C mutations, and the second constant domain comprises the T366S, L368A, K392C, and Y407V mutations; iv. the first constant domain comprises the T366W and K392C mutations, and the second constant domain comprises the T366S, L368A, D399C, and Y407V mutations; v. the first constant domain comprises the S354C and T366W mutations, and the second constant domain comprises the Y349C, T366S, L368A, and Y407V mutations; vi. the first constant domain comprises the Y349C and T366W mutations, and the second constant domain comprises the S354C, T366S, L368A, and Y407V mutations; vii. the first constant domain comprises the E356C and T366W mutations, and the second constant domain comprises the Y349C, T366S, L368A, and Y407V mutations; viii. the first constant domain comprises the Y349C and T366W mutations, and the second constant domain comprises the E356C, T366S, L368A, and Y407V mutations; ix. the first constant domain comprises the E357C and T366W mutations, and the second constant domain comprises the Y349C, T366S, L368A, and Y407V mutations; or x. The first constant domain contains Y349C and T366W mutations, and the second constant domain contains E357C, T366S, L368A and Y407V mutations; and wherein the numbering is according to the EU numbering in human IgG1.

16. The bispecific antibody according to claim 15, wherein the first constant domain contains the T366W mutation, and the second constant domain contains the T366S, L368A and Y407V mutations, wherein the numbering is according to the EU numbering in human IgG1.

17. The bispecific antibody according to claim 16, wherein the first constant domain and the second constant domain contain L234A and L235A (LALA) substitutions, wherein the numbering is according to the EU numbering in human IgG1.

18. The bispecific antibody according to claim 1, wherein: the first polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67; the second polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 79; and the third polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

89.

19. A bispecific antibody, the bispecific antibody comprising: a first polypeptide that comprises the amino acid sequence of SEQ ID NO: 67; a second polypeptide that comprises the amino acid sequence of SEQ ID NO: 79; and a third polypeptide that comprises the amino acid sequence of SEQ ID NO:

89.

20. A pharmaceutical composition, the pharmaceutical composition comprising the bispecific antibody according to claim 1 and a pharmaceutically acceptable excipient.

21. A pharmaceutical composition, the pharmaceutical composition comprising the bispecific antibody according to claim 18 and a pharmaceutically acceptable excipient.

22. A pharmaceutical composition, the pharmaceutical composition comprising the bispecific antibody according to claim 19 and a pharmaceutically acceptable excipient.

23. A nucleic acid molecule or nucleic acid molecules that encode the polypeptide of the bispecific antibody according to claim 1.

24. A cell, the cell comprising one nucleic acid molecule or nucleic acid molecules according to claim 23.

25. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject the bispecific antibody according to claim 1.

26. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject the bispecific antibody according to claim 19.

27. The method according to claim 26, wherein the cancer is non-small cell lung cancer (NSCLC), ovarian cancer, gastric cancer, breast cancer, endometrial cancer or testicular cancer.

28. A composition, the composition comprising a tandem single-chain variable fragment (scFv) specific for claudin 6 and CD3, the tandem single-chain variable fragment (scFv) comprising one or more of the following: I. (a) The amino acid sequence of SEQ ID NO. 82, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO: 7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO: 8 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO: 9 or a variant thereof, and (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 10 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 12 or a variant thereof, II. (a) The amino acid sequence of SEQ ID NO. 83, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:8 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:10 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:11 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:12 or a variant thereof, III. (a) The amino acid sequence of SEQ ID NO.84, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, and (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, IV. (a) The amino acid sequence of SEQ ID NO:85, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, and (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, V. (a) the amino acid sequence of SEQ ID NO.93, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, and (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof, VI. (a) the amino acid sequence of SEQ ID NO.94, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, (ii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 19 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 20 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 21 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant thereof, VII. (a) The amino acid sequence of SEQ ID NO. 95, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, (ii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, VIII. (a) The amino acid sequence of SEQ ID NO. 96, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, (ii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 15 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 25 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 26 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 27 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 28 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 29 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 30 or a variant thereof, IX. (a) The amino acid sequence of SEQ ID NO. 97, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO: 1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, and (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, X. (a) the amino acid sequence of SEQ ID NO.98, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, and (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, XI. (a) The amino acid sequence of SEQ ID NO.99, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (iii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and (iv) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, XII. (a) The amino acid sequence of SEQ ID NO.100, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) a VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein the LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) a VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, XIII. (a) The amino acid sequence of SEQ ID NO:109, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2 and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2 and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, and XIV. (a) The amino acid sequence of SEQ ID NO:110, or an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or (b) (i) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, (iii) A VH comprising HCDR1, HCDR2, and HCDR3 sequences, wherein said HCDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, said HCDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and said HCDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, and (iv) A VL comprising LCDR1, LCDR2, and LCDR3 sequences, wherein said LCDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, said LCDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and said LCDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, or wherein: Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and Any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

29. A composition comprising a scFv-Fab Fc antibody specific for claudin 6 and CD3, said antibody comprising: (a) A first heavy chain selected from: (i) SEQ ID NO:79, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein said heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, said heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and said heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (ii) SEQ ID NO:88, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or (iii) SEQ ID NO:114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof, (b) A second heavy chain selected from: (i.) SEQ ID NO:80, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, or (ii.) SEQ ID NO:89, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof, or (iii.) SEQ ID NO:90, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:48 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, or (iv.) SEQ ID NO:91, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:49 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof, or (v.) SEQ ID NO:92, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, or (vi.) SEQ ID NO:111, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, and (c) A first light chain selected from: (i) SEQ ID NO:67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) SEQ ID NO:66, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or (iii) SEQ ID NO:65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or wherein: Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and Any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

30. A composition, the composition comprising an IgG-(scFV)2 antibody specific for claudin 6 and CD3, the antibody comprising: (a) a heavy chain, the heavy chain selected from: (i.) SEQ ID NO:86, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, (ii.) SEQ ID NO:87, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, (iii.) SEQ ID NO:101, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, (iv.) SEQ ID NO:102, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, (v.) SEQ ID NO:103, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof, (vi.) SEQ ID NO:104, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof, (vii.) SEQ ID NO:105, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, (viii.) SEQ ID NO:106, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, (ix.) SEQ ID NO:107, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof, (x.) SEQ ID NO:108, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof, (xi.) SEQ ID NO:112, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, (xii.) SEQ ID NO:113, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, and (b) A light chain selected from: (i) SEQ ID NO:67, An amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) SEQ ID NO:66, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or (iii) SEQ ID NO:65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or wherein: any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

31. A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising: (a) a first heavy chain selected from: (i) SEQ ID NO:79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (ii) SEQ ID NO:88, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or (iii) SEQ ID NO:114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof, (b) a second heavy chain selected from: SEQ ID NO:81, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, and (c) a light chain selected from: (i) SEQ ID NO:67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) SEQ ID NO:66 an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or (iii) SEQ ID NO:65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or wherein: Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functional equivalent variant thereof.

32. A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising: (a) A first heavy chain selected from: (i) SEQ ID NO:79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (ii) SEQ ID NO:88, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or (iii) SEQ ID NO:114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof, (b) A second heavy chain selected from: (i.) SEQ ID NO:117, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, (ii.) SEQ ID NO:119, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, (iii.) SEQ ID NO:118, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (iv.) SEQ ID NO:120, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2 and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:16 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:17 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:18 or a variant thereof, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, and (c) A light chain selected from: (i) SEQ ID NO:67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) SEQ ID NO:66, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or (iii) SEQ ID NO:65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or wherein: Any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and Any of the above sequences optionally has a linker comprising one or more glycines and serines, which linker is replaced by another peptide linker or a functional equivalent.

33. A composition comprising an scFv-Fab Fc antibody specific for claudin 6 and CD3, the antibody comprising: (a) A first heavy chain selected from: (i) SEQ ID NO:79, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:6 or a variant thereof, (ii) SEQ ID NO:88, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:15 or a variant thereof, or (iii) SEQ ID NO:114, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:4 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:5 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:47 or a variant thereof, (b) A second heavy chain, the second heavy chain being selected from: (i) SEQ ID NO:121, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:26 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:27 or a variant thereof, (ii) SEQ ID NO:123, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:25 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:31 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:32 or a variant thereof, (iii) SEQ ID NO:125, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:19 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:20 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:21 or a variant thereof, (iv) SEQ ID NO:127, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:7 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:36 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:9 or a variant thereof, (v) SEQ ID NO:129, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO:40 or a variant thereof, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO:41 or a variant thereof, and the heavy chain CDR3 comprises the amino acid sequence of SEQ ID NO:42 or a variant thereof, and (c) a first light chain, the first light chain selected from: (i) SEQ ID NO:67, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, (ii) SEQ ID NO:66, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:13 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:14 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof, or (iii) SEQ ID NO:65, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:1 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:2 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:3 or a variant thereof and (d) a second light chain selected from: (i) SEQ ID NO:122, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:28 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:29 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:30 or a variant thereof, or (ii) SEQ ID NO:124, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:33 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:34 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:35 or a variant thereof, or (iii) SEQ ID NO:126, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 comprises the amino acid sequence of SEQ ID NO:22 or a variant thereof, the light chain CDR2 comprises the amino acid sequence of SEQ ID NO:23 or a variant thereof, and the light chain CDR3 comprises the amino acid sequence of SEQ ID NO:24 or a variant thereof, or (iv) SEQ ID NO:128, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or A light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:37 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:38 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:39 or a variant thereof, or (v) SEQ ID NO:130, an amino acid sequence having at least about 90%, or about 93%, or about 95%, or about 97%, or about 98%, or about 99% identity thereto, or a light chain variable region comprising light chain CDR1, CDR2 and CDR3 sequences, wherein said light chain CDR1 comprises the amino acid sequence of SEQ ID NO:43 or a variant thereof, said light chain CDR2 comprises the amino acid sequence of SEQ ID NO:44 or a variant thereof, and said light chain CDR3 comprises the amino acid sequence of SEQ ID NO:45 or a variant thereof, or wherein: any of the above sequences in sub-item (a) may optionally have a His6 tag (e.g., HHHHHH (SEQ ID NO:46)) added to the N-terminus or C-terminus, and any of the above sequences optionally has a linker comprising one or more glycines and serines, and the linker is replaced by another peptide linker or a functionally equivalent variant thereof.

34. The composition according to any one of claims 29 to 33, wherein the composition binds both claudin 6 and CD3 simultaneously.

35. The composition according to any one of claims 29 to 34, wherein the composition binds claudin 6 with an affinity of less than 10 nM and an affinity at least 100-fold that for claudin 9, claudin 3 and / or claudin 4.

36. A pharmaceutical composition comprising the isolated antibody according to any one of claims 29 to 34 or a nucleic acid molecule encoding said antibody.

37. A nucleic acid molecule encoding the antibody or amino acid sequence according to any one of claims 29 to 34.

38. A vector comprising the nucleic acid molecule according to claim 37.

39. A cell comprising the nucleic acid molecule according to claim 37 or the vector according to claim 38.

40. A method for treating or preventing cancer, the method comprising administering to a subject in need thereof an effective amount of the composition according to any one of claims 29 to 34.

41. Use of the bispecific antibody according to any one of claims 1 to 19 or the composition according to any one of claims 29 to 34 in the preparation of a medicament for treating cancer.

42. The method or use according to claim 40 or 41, wherein the cancer is selected from one or more of the following: basal cell carcinoma; biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; peritoneal cancer; cervical cancer; choriocarcinoma; colon and rectal cancer; connective tissue cancer; digestive system cancer; endometrial cancer; esophageal cancer; eye cancer; head and neck cancer; gastric cancer (including gastrointestinal cancer); glioblastoma; glioma; liver cancer; hepatocellular carcinoma; intraepithelial neoplasia; kidney cancer or renal carcinoma; laryngeal cancer; leukemia; liver cancer; lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and squamous cell lung cancer); melanoma; myeloma; neuroblastoma; oral cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; malignant rhabdoid tumor; rectal cancer; respiratory system cancer; salivary gland cancer; sarcoma; skin cancer; squamous cell carcinoma; gastric cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; urinary system cancer; vulvar cancer; lymphoma, including Hodgkin's and non-Hodgkin's lymphoma, and B-cell lymphoma (including low-grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate / follicular NHL; intermediate diffuse NHL; high-grade immunoblastic NHL; high-grade lymphoblastic NHL; high-grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenström's macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphocytic leukemia (ALL); hairy cell leukemia; chronic myelogenous leukemia; and other carcinomas and sarcomas; and post-transplant lymphoproliferative disorder (PTLD), and abnormal vascular proliferation associated with nevus flammeus, edema (e.g., edema associated with brain tumors), and Meigs' syndrome.

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